Genomes and Genes
Gene Symbol: Smad4
Description: SMAD family member 4
Alias: AW743858, D18Wsu70e, DPC4, Madh4, mothers against decapentaplegic homolog 4, MAD homolog 4, Smad 4, deletion target in pancreatic carcinoma 4 homolog, mothers against DPP homolog 4
Publications126 found, 100 shown here
- A phylogenetically conserved cis-regulatory module in the Msx2 promoter is sufficient for BMP-dependent transcription in murine and Drosophila embryosSean M Brugger
Department of Biochemistry and Molecular Biology, Norris Cancer Hospital, USC Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
Development 131:5153-65. 2004....
- TGF-β signaling via Smad4 drives IL-10 production in effector Th1 cells and reduces T-cell trafficking in EAEDavid J Huss
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University Medical Center, Columbus, OH, USA
Eur J Immunol 41:2987-96. 2011..Additionally, TGF-β signaling causes binding of Smad4 to the IL-10 promoter, providing molecular evidence for TGF-β-mediated IL-10 production from Th1 effector cells...
- The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryoC Sirard
Amgen Institute, Toronto, Ontario M5G 2C1, Canada
Genes Dev 12:107-19. 1998Mutations in the SMAD4/DPC4 tumor suppressor gene, a key signal transducer in most TGFbeta-related pathways, are involved in 50% of pancreatic cancers. Homozygous Smad4 mutant mice die before day 7.5 of embryogenesis...
- Targeted disruption in murine cells reveals variable requirement for Smad4 in transforming growth factor beta-related signalingC Sirard
Amgen Institute Ontario Cancer Institute, Toronto, Ontario M5G 2C1, Canada
J Biol Chem 275:2063-70. 2000The tumor suppressor gene Smad4 has been proposed to be a common mediator of transforming growth factor beta (TGFbeta)-related signaling pathways...
- Cyclooxygenase 2- and prostaglandin E(2) receptor EP(2)-dependent angiogenesis in Apc(Delta716) mouse intestinal polypsHiroshi Seno
Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto 606 8501, Japan
Cancer Res 62:506-11. 2002..We scored MVD also in several compound mutants carrying Apc(Delta716), namely, mice with an additional mutation in Smad4, in which the polyps progress into invasive adenocarcinomas; mice with a cyclooxygenase (COX)-2 gene (Ptgs2) ..
- Serrated adenomas and mixed polyposis caused by a splice acceptor deletion in the mouse Smad4 genePeter Hohenstein
Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
Genes Chromosomes Cancer 36:273-82. 2003..here referred to as Sad (serrated adenomas), caused by a spontaneously risen splice site mutation in the murine Smad4 gene. The Sad chromosomal region was identified by genetic linkage and loss of heterozygosity (LOH) analysis...
- Cerebellar deficits and hyperactivity in mice lacking Smad4Yong Xing Zhou
Mammalian Genetics Section, National Institute of Diabetes and Digestive and Kidney Diseases NIH, Bethesda, MD 20892, USA
J Biol Chem 278:42313-20. 2003b>Smad4 is a central mediator of TGF-beta signals, which are known to play essential roles in many biological processes...
- A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expressionRui Hong Wang
Genetics of Development and Disease Branch, 10 9N105, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Cell Metab 2:399-409. 2005..Here, we show that a Cre-loxP-mediated liver-specific disruption of SMAD4 results in markedly decreased hepcidin expression and accumulation of iron in many organs, which is most ..
- Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancerNabeel Bardeesy
Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
Genes Dev 20:3130-46. 2006b>SMAD4 is inactivated in the majority of pancreatic ductal adenocarcinomas (PDAC) with concurrent mutational inactivation of the INK4A/ARF tumor suppressor locus and activation of the KRAS oncogene...
- Smad4 is critical for self-renewal of hematopoietic stem cellsGoran Karlsson
Department of Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine, Lund University Hospital and Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, 22184 Lund, Sweden
J Exp Med 204:467-74. 2007..Working at a common level of convergence for all TGF-beta superfamily signals, Smad4 is key in orchestrating these effects...
- SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasionTakanori Kitamura
Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
Nat Genet 39:467-75. 2007Inactivation of TGF-beta family signaling is implicated in colorectal tumor progression. Using cis-Apc(+/Delta716) Smad4(+/-) mutant mice (referred to as cis-Apc/Smad4), a model of invasive colorectal cancer in which TGF-beta family ..
- Essential role of endothelial Smad4 in vascular remodeling and integrityYu Lan
Genetic Laboratory of Development and Diseases, Institute of Biotechnology, 20 Dongdajie, Beijing 100071, People s Republic of China
Mol Cell Biol 27:7683-92. 2007..To investigate the role of endothelial Smad4 in vascular development, we deleted the Smad4 gene specifically in ECs using the Cre-LoxP system...
- Inactivation of Smad4 accelerates Kras(G12D)-mediated pancreatic neoplasiaKyoko Kojima
Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
Cancer Res 67:8121-30. 2007..almost uniformly present in early-stage disease, with subsequent inactivating mutations in p16(INK4A), p53, and SMAD4 occurring in more advanced lesions...
- Molecular antagonism and plasticity of regulatory and inflammatory T cell programsXuexian O Yang
Department of Immunology, M D Anderson Cancer Center, Houston, TX 77030, USA
Immunity 29:44-56. 2008..Although TGF-beta receptor I signaling was required for both Foxp3 and IL-17 induction, SMAD4 was only involved in Foxp3 upregulation...
- Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progressionKristina E Hoot
Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, Oregon 97239 2999, USA
J Clin Invest 118:2722-32. 2008..b>Smad4-/- mouse epidermis develops spontaneous skin squamous cell carcinomas (SCCs), and Smad3-/- mice are resistant to ..
- Smad4-dependent desmoglein-4 expression contributes to hair follicle integrityPhilip Owens
Department of Otolaryngology, Oregon Health Sciences University, Portland, OR 97239, USA
Dev Biol 322:156-66. 2008We have previously shown that keratinocyte-specific deletion of Smad4, a TGFbeta/Activin/BMP signaling mediator, results in a progressive alopecia...
- Ectodermal Smad4 and p38 MAPK are functionally redundant in mediating TGF-beta/BMP signaling during tooth and palate developmentXun Xu
Center for Craniofacial Molecular Biology, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA
Dev Cell 15:322-9. 2008b>Smad4 is a central intracellular effector of TGF-beta signaling. Smad-independent TGF-beta pathways, such as those mediated by p38 MAPK, have been identified in cell culture systems, but their in vivo functional mechanisms remain unclear...
- Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokinesJens Nolting
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
J Exp Med 206:2131-9. 2009..Interleukin (IL)-6 strongly reduced RAR alpha expression levels such that a deficiency of the predominant RAR alpha 1 isoform leaves too little RAR alpha 2 for RA to inhibit the generation of Th17 cells in the presence of IL-6...
- BMP signaling regulates sympathetic nervous system development through Smad4-dependent and -independent pathwaysYuka Morikawa
Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA
Development 136:3575-84. 2009..To determine if Alk3 signals through the canonical BMP pathway, Smad4 was deleted in the NC lineage...
- Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammationSophia Bornstein
Department of Otolaryngology, Oregon Health and Science University OHSU, Portland, Oregon, USA
J Clin Invest 119:3408-19. 2009b>Smad4 is a central mediator of TGF-beta signaling, and its expression is downregulated or lost at the malignant stage in several cancer types...
- Synergistic action of Smad4 and Pten in suppressing pancreatic ductal adenocarcinoma formation in miceX Xu
Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Oncogene 29:674-86. 2010Mutations of SMAD4/DPC4 are found in about 60% of human invasive pancreatic ductal adenocarcinomas (PDACs); yet, the manner in which SMAD4 deficiency enhances tumorigenesis remains elusive...
- HGF upregulation contributes to angiogenesis in mice with keratinocyte-specific Smad2 deletionKristina E Hoot
Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, Oregon, USA
J Clin Invest 120:3606-16. 2010..On the Hgf promoter, Smad2 was mainly associated with transcriptional corepressors, whereas Smad4 was mainly associated with the transcriptional coactivator CREB-binding protein (CBP/p300)...
- Smad4-mediated signaling inhibits intestinal neoplasia by inhibiting expression of β-cateninTanner J Freeman
Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232 2730, USA
Gastroenterology 142:562-571.e2. 2012..However, the interactions between these pathways are not clear. We investigated the effects of loss of the transcription factor Smad4 on levels of β-catenin messenger RNA (mRNA) and Wnt signaling.
- Vascular smooth muscle cell Smad4 gene is important for mouse vascular developmentXia Mao
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
Arterioscler Thromb Vasc Biol 32:2171-7. 2012b>Smad4 is a central mediator of transforming growth factor-β/bone morphogenetic protein signaling that controls numerous developmental processes as well as homeostasis in the adult...
- Smad4 is required to induce digit ray primordia and to initiate the aggregation and differentiation of chondrogenic progenitors in mouse limb budsJean Denis Bénazet
Developmental Genetics, Department of Biomedicine, University of Basel, Mattenstrasse 28, Basel, Switzerland
Development 139:4250-60. 2012b>SMAD4 is an essential mediator of canonical TGFβ/BMP signal transduction and we inactivated Smad4 in mouse limb buds from early stages onward to study its functions in the mesenchyme...
- TGF-beta signalling from cell membrane to nucleus through SMAD proteinsC H Heldin
Ludwig Institute for Cancer Research, Biomedical Centre, Uppsala, Sweden
Nature 390:465-71. 1997..cell-surface receptors that have serine/threonine kinase activity, then they oligomerize with the common mediator Smad4 and translocate to the nucleus where they direct transcription to effect the cell's response to TGF-beta...
- Smad2 signaling in extraembryonic tissues determines anterior-posterior polarity of the early mouse embryoW R Waldrip
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Cell 92:797-808. 1998..Chimera experiments demonstrate these essential activities are contributed by the extraembryonic tissues. Thus, the extraembryonic tissues play critical roles in establishing the body plan during early mouse development...
- Gastric and duodenal polyps in Smad4 (Dpc4) knockout miceK Takaku
Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Japan
Cancer Res 59:6113-7. 1999The SMAD4 (DPC4) gene was initially isolated as a candidate tumor suppressor from the convergent site of homozygous deletions on 18q in a panel of pancreatic carcinoma cell lines...
- Functions of mammalian Smad genes as revealed by targeted gene disruption in miceM Weinstein
Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 9N105, 10 Center Drive, Bethesda, MD 20892, USA
Cytokine Growth Factor Rev 11:49-58. 2000..These experiments have shown that Smad2 and Smad4 are needed for gastrulation, Smad5 for angiogenesis, and Smad3 for establishment of the mucosal immune response ..
- Haploid loss of the tumor suppressor Smad4/Dpc4 initiates gastric polyposis and cancer in miceX Xu
Genetics of Development and Disease Branch, 10 9N105, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, MD 20892, USA
Oncogene 19:1868-74. 2000The tumor suppressor SMAD4, also known as DPC4, deleted in pancreatic cancer, is a central mediator of TGF-beta signaling...
- Generation of Smad4/Dpc4 conditional knockout miceXiao Yang
Genetics of Development and Disease Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
Genesis 32:80-1. 2002
- Squamous cell carcinoma and mammary abscess formation through squamous metaplasia in Smad4/Dpc4 conditional knockout miceWenmei Li
Genetics of Development and Disease Branch, NIDDK, NIH, 10 9N105, 10 Center Drive, Bethesda, MD 20892, USA
Development 130:6143-53. 2003b>Smad4 is a central mediator for TGFbeta signals, which play important functions in many biological processes...
- Targeted disruption of Smad4 in cardiomyocytes results in cardiac hypertrophy and heart failureJian Wang
Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, People s Republic of China
Circ Res 97:821-8. 2005..b>Smad4 is the central intracellular mediator of TGF-beta signaling...
- Targeted disruption of Smad4 in mouse epidermis results in failure of hair follicle cycling and formation of skin tumorsLeilei Yang
Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Shanghai, P R China
Cancer Res 65:8671-8. 2005b>Smad4 is the common mediator of transforming growth factor-beta (TGF-beta) superfamily signaling, which functions in diverse developmental processes in mammals...
- Smad4 haploinsufficiency in mouse models for intestinal cancerP Alberici
Department of Pathology, Josephine Nefkens Institute, ErasmusMC, Rotterdam, The Netherlands
Oncogene 25:1841-51. 2006The Smad4(+/E6sad) mouse carries a null mutation in the endogenous Smad4 gene resulting in serrated adenomas and mixed polyposis of the upper gastrointestinal (GI) tract with 100% penetrance...
- Isl1Cre reveals a common Bmp pathway in heart and limb developmentLei Yang
Skaggs School of Pharmacy, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Development 133:1575-85. 2006..Tbx3 is required for heart and limb formation, and is mutated in ulnar-mammary syndrome. We provide evidence that the Tbx3 promoter is directly regulated by Bmp Smads in vivo...
- Smad4 signalling in T cells is required for suppression of gastrointestinal cancerByung Gyu Kim
Laboratory of Cell Regulation and Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Nature 441:1015-9. 2006b>SMAD4 (MAD homologue 4 (Drosophila)), also known as DPC4 (deleted in pancreatic cancer), is a tumour suppressor gene that encodes a central mediator of transforming growth factor-beta signalling...
- Mice develop normally in the absence of Smad4 nucleocytoplasmic shuttlingChristine A Biondi
The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Biochem J 404:235-45. 2007b>Smad4 in partnership with R-Smads (receptor-regulated Smads) activates TGF-beta (transforming growth factor-beta)-dependent signalling pathways essential for early mouse development...
- Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreasKamel Izeradjene
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Cancer Cell 11:229-43. 2007..We show here that concomitant expression of Kras(G12D) and haploinsufficiency of the Smad4/Dpc4 tumor suppressor gene engenders a distinct class of pancreatic tumors, mucinous cystic neoplasms (MCNs), ..
- Smad4 is required for maintaining normal murine postnatal bone homeostasisXiaohong Tan
Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, PR China
J Cell Sci 120:2162-70. 2007Transforming growth factor beta (TGFbeta) is a multifunctional cytokine involved in skeletal development. Smad4 is the central intracellular mediator of TGFbeta signaling...
- Myocardial smad4 is essential for cardiogenesis in mouse embryosLanying Song
Department of Genetics, Division of Genetic and Translational Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
Circ Res 101:277-85. 2007..b>Smad4 encodes the only common Smad protein in mammals, which is a critical nuclear mediator of transforming growth ..
- Smad4 is required to regulate the fate of cranial neural crest cellsSeung O Ko
Center for Craniofacial Molecular Biology School of Dentistry University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA
Dev Biol 312:435-47. 2007b>Smad4 is the central mediator for TGF-beta/BMP signals, which are involved in regulating cranial neural crest (CNC) cell formation, migration, proliferation and fate determination...
- TGF-beta signaling is dynamically regulated during the alveolarization of rodent and human lungsMiguel A Alejandre-Alcázar
Department of Internal Medicine, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
Dev Dyn 237:259-69. 2008..TGF-beta receptors Acvrl1, Tgfbr1, Tgfbr2, Tgfbr3, and endoglin, and the intracellular messengers Smad2, Smad3, Smad4, Smad6, and Smad7 were noted as mouse and human lungs progressed through the canalicular, saccular, and alveolar ..
- Disruption of Smad4 in neural crest cells leads to mid-gestation death with pharyngeal arch, craniofacial and cardiac defectsXuguang Nie
Department of Genetics, Division of Genetic and Translational Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
Dev Biol 316:417-30. 2008TGFbeta/BMP signaling pathways are essential for normal development of neural crest cells (NCCs). Smad4 encodes the only common Smad protein in mammals, which is a critical nuclear mediator of TGFbeta/BMP signaling...
- Multiple lineage-specific roles of Smad4 during neural crest developmentStine Büchmann-Møller
Division of Cell and Developmental Biology, Institute of Anatomy, University of Zurich, CH 8057 Zurich, Switzerland
Dev Biol 330:329-38. 2009..To address these issues, we conditionally deleted Smad4 in the neural crest, thus inactivating all canonical TGFbeta factor signaling...
- SMAD4-dependent barrier constrains prostate cancer growth and metastatic progressionZhihu Ding
Belfer Institute for Applied Cancer Science, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
Nature 470:269-73. 2011..epithelium versus poorly progressive Pten-null prostate cancers revealed robust activation of the TGFβ/BMP-SMAD4 signalling axis...
- Smad4 deficiency in T cells leads to the Th17-associated development of premalignant gastroduodenal lesions in miceJennifer Nancy Hahn
Department of Biochemistry and Molecular Biology, The McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada
J Clin Invest 121:4030-42. 2011..Here, we employed two conditional mutagenesis systems to delete the TGF-β signaling pathway component Smad4 in T cells and observed the spontaneous development of massive polyps within the gastroduodenal regions of mice...
- Disruption of Smad4 impairs TGF-β/Smad3 and Smad7 transcriptional regulation during renal inflammation and fibrosis in vivo and in vitroXiao ming Meng
Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR China
Kidney Int 81:266-79. 2012..Following activation, these Smads form heteromeric complex with Smad4 and translocate into the nucleus to bind and regulate the expression of target genes...
- Absence of canonical Smad signaling in ureteral and bladder mesenchyme causes ureteropelvic junction obstructionPiyush Tripathi
Renal Division, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
J Am Soc Nephrol 23:618-28. 2012..To study the molecular mechanisms that modulate ureteral development, we inactivated Smad4, the common Smad critical for transcriptional responses to TGF-β and Bmp signaling, in the ureteral and bladder ..
- SMAD4 loss triggers the phenotypic changes of pancreatic ductal adenocarcinoma cellsYu Wen Chen
Institute of Biomedical Sciences, National Sun Yat Sen University, Kaohsiung 80424, Taiwan
BMC Cancer 14:181. 2014b>SMAD4 is a gastrointestinal malignancy-specific tumor suppressor gene found mutated in one third of colorectal cancer specimens and half of pancreatic tumors...
- The tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and mesoderm induction in miceX Yang
Laboratory of Biochemistry and Metabolism, 10 9N105, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 95:3667-72. 1998..The tumor suppressor SMAD4, also known as DPC4, is believed to be an essential factor that mediates TGF-beta signals...
- Differential requirements for Smad4 in TGFbeta-dependent patterning of the early mouse embryoGerald C Chu
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Development 131:3501-12. 2004Genetic and biochemical data have identified Smad4 as a key intracellular effector of the transforming growth factor beta (TGFbeta superfamily of secreted ligands...
- Hair follicle defects and squamous cell carcinoma formation in Smad4 conditional knockout mouse skinW Qiao
Genetics of Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Oncogene 25:207-17. 2006b>Smad4 is the common mediator for TGFbeta signals, which play important functions in many biological processes...
- Essential role of Smad4 in maintaining cardiomyocyte proliferation during murine embryonic heart developmentXin Qi
State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Beijing Institute of Biotechnology, 20 Dongdajie, Fengtai, Beijing 100071, PR China
Dev Biol 311:136-46. 2007..The intracellular factor Smad4 plays a pivotal role in mediating TGF-beta/BMP signal transduction in the nucleus...
- Smad signaling in the neural crest regulates cardiac outflow tract remodeling through cell autonomous and non-cell autonomous effectsQunshan Jia
Renal Division, Department of Internal Medicine, Department of Cell Biology and Physiology, Campus Box 8126, Washington University School of Medicine, St Louis, MO 63110, USA
Dev Biol 311:172-84. 2007..Here, we show that mice lacking Smad4 in NCCs have persistent truncus arteriosus (PTA), severe OFT cushion hypoplasia, defective OFT elongation, and ..
- Cell fate decisions within the mouse organizer are governed by graded Nodal signalsStephane D Vincent
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Genes Dev 17:1646-62. 2003..These findings conclusively demonstrate that graded Nodal/Smad2 signals govern allocation of the axial mesendoderm precursors that selectively give rise to the ADE and PCP mesoderm...
- Ectopic expression of the transforming growth factor beta type II receptor disrupts mesoderm organisation during mouse gastrulationA Zwijsen
Hubrecht Laboratory, Netherlands Institute of Developmental Biology, Utrecht
Dev Dyn 214:141-51. 1999....
- Mechanisms of TGFbeta inhibition of LUNG endodermal morphogenesis: the role of TbetaRII, Smads, Nkx2.1 and PtenYiming Xing
Department of Pediatrics, Division of Neonatology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA
Dev Biol 320:340-50. 2008..by TGFbeta was partially abrogated in endodermal explants from Smad3(-/-) or conditional endodermal-specific Smad4(Delta/Delta) embryonic lungs...
- Collagen1alpha1 promoter drives the expression of Cre recombinase in osteoblasts of transgenic miceLagabaiyila Zha
State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, China
J Genet Genomics 35:525-30. 2008..mice, the Col1alpha1-Cre transgenic mice were bred with the ROSA26 reporter strain and a mouse strain that carries Smad4 conditional alleles (Smad4(Co/Co))...
- 4E-BP1 is a target of Smad4 essential for TGFbeta-mediated inhibition of cell proliferationRania Azar
INSERM U858, Institut de Médecine Moléculaire de Rangueil I2MR, Toulouse, France
EMBO J 28:3514-22. 2009..Here, we show that Smad4, a transcription factor normally required for TGFbeta-mediated inhibition of normal cell proliferation, enhances ..
- Smad4 binds Hoxa9 in the cytoplasm and protects primitive hematopoietic cells against nuclear activation by Hoxa9 and leukemia transformationRonan Quere
Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund, Sweden
Blood 117:5918-30. 2011We studied leukemic stem cells (LSCs) in a Smad4(-/-) mouse model of acute myelogenous leukemia (AML) induced either by the HOXA9 gene or by the fusion oncogene NUP98-HOXA9...
- AGR2 is a SMAD4-suppressible gene that modulates MUC1 levels and promotes the initiation and progression of pancreatic intraepithelial neoplasiaA M Norris
Department of Medicine, Dartmouth Medical School, Hanover, NH, USA
Oncogene 32:3867-76. 2013..a transforming growth factor-β (TGF-β)-responsive gene in human pancreatic cancer cells, whose downregulation is SMAD4 dependent...
- TGFβ signaling regulates the timing of CNS myelination by modulating oligodendrocyte progenitor cell cycle exit through SMAD3/4/FoxO1/Sp1Javier Palazuelos
Department of Pharmacological Sciences, Center for Molecular Medicine and
J Neurosci 34:7917-30. 2014..Our study is the first to demonstrate an autonomous and crucial role of TGFβ signaling in OL development and CNS myelination, and may provide new avenues in the treatment of demyelinating diseases. ..
- Minimal fertility defects in mice deficient in oocyte-expressed Smad4Xiaohui Li
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
Biol Reprod 86:1-6. 2012..Deletion in granulosa cells of Smad4, the common SMAD mediating all canonical TGFB-related protein signals, results in infertility...
- Tif1γ suppresses murine pancreatic tumoral transformation by a Smad4-independent pathwayDavid F Vincent
INSERM U1052, Cancer Research Center of Lyon CRCL, Lyon, France
Am J Pathol 180:2214-21. 2012..Deletion of SMAD4/DPC4 (deleted in pancreatic carcinoma locus 4) occurs in approximately 50% of human cases of PDAC...
- [Histological changes of peripheral vestibular organs in the inner ears of Smad4 conditional knockout mice]An Chun Deng
Department of Otorhinolaryngology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 47:575-80. 2012To investigate the histological changes in the vestibular endorgans of Smad4 gene conditional knockout mice and to explore the influence of the Smad4 gene on vestibular development.
- SMAD4 haploinsufficiency associates with augmented colonic inflammation in select humans and miceReka Szigeti
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA
Ann Clin Lab Sci 42:401-8. 2012b>SMAD4 is a common mediator of the TGF-beta signaling pathway. One of the members of this pathway, TGF-beta 1, has an important role in controlling gut inflammation in relation to the continuous stimulation of the intestinal microbiota...
- Smad4-Irf6 genetic interaction and TGFβ-mediated IRF6 signaling cascade are crucial for palatal fusion in miceJun ichi Iwata
Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA
Development 140:1220-30. 2013..Haploinsufficiency of Irf6 in mice with basal epithelial-specific deletion of the TGFβ signaling mediator Smad4 (Smad4(fl/fl);K14-Cre;Irf6(+/R84C)) results in compromised p21 expression and MEE persistence, similar to ..
- Smad signaling pathways regulate pancreatic endocrine developmentYousef El-Gohary
Department of Surgery, Division of Pediatric Surgery, Children s Hospital of Pittsburgh, One Children s Hospital Drive, 4401 Penn Ave, Pittsburgh, PA 15224, USA
Dev Biol 378:83-93. 2013..These results should provide a better understanding of the key control mechanisms for β-cell development...
- Smad4 and FAST-1 in the assembly of activin-responsive factorX Chen
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115 5730, USA
Nature 389:85-9. 1997..Activins are growth factors that act primarily through Smad2, possibly in partnership with Smad4, which forms heteromeric complexes with different ligand-specific SMADs after activation...
- Genetic events and the role of TGF beta in epithelial tumour progressionR J Akhurst
Onyx Pharmaceuticals, Richmond, CA 94806, USA
J Pathol 187:82-90. 1999..It is this latter effect which may be clinically more significant, since many human tumours overexpress TGF beta, yet the majority still retain the intracellular signaling systems necessary for the cell to respond to this growth factor...
- Can't get no SMADisfaction: Smad proteins as positive and negative regulators of TGF-beta family signalsJ L Christian
Department of Cell and Developmental Biology, Oregon Health Sciences University, School of Medicine, Portland 97201 3098, USA
Bioessays 21:382-90. 1999..Negative feedback circuits such as these play important roles in fine-tuning the activity of multifunctional signaling molecules during embryonic patterning and in response to pathologic stimuli in adults...
- Gastro-intestinal tumorigenesis in Smad4 mutant miceM M Taketo
Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
Cytokine Growth Factor Rev 11:147-57. 2000The SMAD4 gene plays a key role in the TGF-beta signaling pathway. We inactivated its mouse homolog Smad4. The homozygous mutants were embryonically lethal, whereas the heterozygotes were viable and fertile...
- Gastrointestinal tumorigenesis in Smad4 (Dpc4) mutant miceM M Taketo
Department of Pharmacology, Graduate School of Medicine Kyoto University, Yoshida konoe cho, Sakyo ku, Kyoto 606 8501 Japan
Hum Cell 13:85-95. 2000The SMAD4 (Dpc4) gene plays a key role in the TGF-beta signaling pathway. We recently inactivated the mouse homolog Smad4. The homozygous mutants were embryonic lethals, whereas the heterozygotes were viable and fertile...
- Dynamic regulation of Smad expression during mesenchyme to epithelium transition in the metanephric kidneyLeif Oxburgh
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
Mech Dev 112:207-11. 2002..chloride to promote condensation in isolated cultured mesenchymal explants and subsequently assayed expression of Smad 4. Down-regulation is complete in lithium chloride induced mesenchymal condensates, indicating that Smad regulation ..
- A central role for the JNK pathway in mediating the antagonistic activity of pro-inflammatory cytokines against transforming growth factor-beta-driven SMAD3/4-specific gene expressionFranck Verrecchia
INSERM U532, Institut de Recherche sur la Peau Hôpital Saint Louis, 75475 Paris Cedex 10, France
J Biol Chem 278:1585-93. 2003..In addition, we demonstrate that such a JNK-dependent regulatory mechanism underlies the antagonistic activity of TNF-alpha against TGF-beta-induced up-regulation of type I and III collagens in fibroblasts...
- Transforming growth factor-beta inhibits adipocyte differentiation by Smad3 interacting with CCAAT/enhancer-binding protein (C/EBP) and repressing C/EBP transactivation functionLisa Choy
Department of Growth and Development, Programs in Cell Biology and Developmental Biology, University of California, San Francisco, California 94143 0640, USA
J Biol Chem 278:9609-19. 2003..inhibits adipogenesis by signaling through Smad3, we examined physical and functional interactions of Smad3 and Smad4 with C/EBPbeta, C/EBPdelta, and PPARgamma2...
- A major locus on mouse chromosome 18 controls XX sex reversal in Odd Sex (Ods) miceYangjun Qin
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA
Hum Mol Genet 12:509-15. 2003..The close proximity of Smad2, Smad7 and Smad4 to D18Mit189/210 provides a potential mechanism through which Odsm1 might act.
- The gonadotropin releasing hormone (GnRH) receptor activating sequence (GRAS) is a composite regulatory element that interacts with multiple classes of transcription factors including Smads, AP-1 and a forkhead DNA binding proteinBuffy S Ellsworth
Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
Mol Cell Endocrinol 206:93-111. 2003..Consistent with activin regulation at GRAS, gel shift analyses and yeast one-hybrid assays reveal Smad4 interaction at the 5' end of GRAS...
- Interaction of Smads with collagen types I, III, and VLeslie R Ellis
Department of Molecular, Cellular, and Craniofacial Biology, ULSD, University of Louisville Birth Defects Center, Louisville, KY 40292, USA
Biochem Biophys Res Commun 310:1117-23. 2003..Moreover, TGFbeta is a potent regulator of collagen synthesis and turnover during mammalian orofacial development. These data thus suggest an important means of feedback regulation of the TGFbeta signaling cascade...
- Identification of novel Smad binding proteinsDennis R Warner
Department of Molecular, Cellular, and Craniofacial Biology, University of Louisville Birth Defects Center, ULSD, Louisville, KY 40292, USA
Biochem Biophys Res Commun 312:1185-90. 2003..The identification of these proteins as Smad binding partners allows exploration of new mechanisms whereby TGFbeta signaling may be regulated, and reveals additional potential interactions with other signaling pathways...
- TGFbeta3 signaling activates transcription of the LEF1 gene to induce epithelial mesenchymal transformation during mouse palate developmentAli Nawshad
Department of Cell Biology, Harvard Medical School, 220 Longwood Ave, B 1, Room 342, Boston, MA 02115 6092, USA
J Cell Biol 163:1291-301. 2003..out other TGFbeta3 targets, such as RhoA and MEK1/2 pathways, and we present evidence using dominant-negative Smad4 and dominant-negative LEF1 showing that TGFbeta3 uses Smads both to up-regulate synthesis of LEF1 and to activate ..
- Simultaneous expression of COX-2 and mPGES-1 in mouse gastrointestinal hamartomasH Takeda
Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto 606 8501, Japan
Br J Cancer 90:701-4. 2004..COX-2 and microsomal prostaglandin E(2) synthase (mPGES)-1 in gastrointestinal hamartomas developed in Lkb1(+/-), Smad4(+/-) and Cdx2(+/-)mice...
- Induction of vascular smooth muscle alpha-actin gene transcription in transforming growth factor beta1-activated myofibroblasts mediated by dynamic interplay between the Pur repressor proteins and Sp1/Smad coactivatorsSukanya V Subramanian
Department of Physiology and Cell Biology, Dorothy M Davis Heart and Lung Research Institute, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210, USA
Mol Biol Cell 15:4532-43. 2004..Interplay between Pur repressor isoforms and Sp1 and Smad coactivators may regulate SMA enhancer output in TGFbeta1-activated myofibroblasts during episodes of wound repair and tissue remodeling...
- Orofacial and gastrointestinal hyperplasia and neoplasia in smad4+/- and elf+/-/smad4+/- mutant miceRobert S Redman
Oral Pathology Research Laboratory, Department of Veterans Affairs Medical Center, Washington, DC 20422, USA
J Oral Pathol Med 34:23-9. 2005b>Smad4 is vital to the roles of Smads 2 and 3 in transforming growth factor-beta (TGF)-beta signal transduction, and inactivated Smad4 is common to human gastrointestinal cancers...
- Glypican-3 modulates inhibitory Bmp2-Smad signaling to control renal development in vivoSunny Hartwig
Program in Developmental Biology, Research Institute, The Hospital for Sick Children, Toronto, Canada
Mech Dev 122:928-38. 2005..models of branching morphogenesis, we demonstrated that BMP2 signals via its intracellular effectors, SMAD1 and SMAD4, to control UB cell proliferation and branching in a manner modulated by Glypican-3 (GPC3), a cell surface heparan ..
- Islet hypertrophy following pancreatic disruption of Smad4 signalingDiane M Simeone
Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA
Am J Physiol Endocrinol Metab 291:E1305-16. 2006..signaling in the adult pancreas, a transgenic mouse (E-dnSmad4) was created that expresses a dominant-negative Smad4 protein driven by a fragment of the elastase promoter...
- Localization of TGF-beta signaling intermediates Smad2, 3, 4, and 7 in developing and mature human and mouse kidneyMiriam C Banas
Klinik und Poliklinik fur Innere Medizin II, Franz Josef Strauss Allee 11, 93053 Regensburg, Germany
J Histochem Cytochem 55:275-85. 2007..We studied the expression of TGF-beta-receptor activated Smads (Smad2 and Smad3), the common partner Smad (Smad4), an inhibitory Smad (Smad7), and the activated (phosphorylated) Smad2 (pSmad2) in developing and adult kidneys of ..
- A role for TGF-beta signaling in neurodegeneration: evidence from genetically engineered modelsIna Tesseur
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
Curr Alzheimer Res 3:505-13. 2006..Future studies will have to determine whether dysregulation of TGF-beta signaling in neurodegenerative diseases is significant and whether this signaling pathway may even be a target for treatment...
- SMAD expression in the testis: an insight into BMP regulation of spermatogenesisCatherine Itman
Monash Institute of Medical Research, and the Australian Research Council Centre of Excellence in Biotechnology and Development, Monash University, Melbourne, Victoria, Australia
Dev Dyn 237:97-111. 2008..Smad1, Smad5, Smad8, Smad4, Smad6, and Smad7 expression is ubiquitous during testis development but becomes cell-specific in the adult...
- [Hematopoiesis is normally maintained in osteoblast-specific Smad4 gene knockout mice]Yu Lan
Department of Development and Genetics, Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, China
Zhongguo Shi Yan Xue Ye Xue Za Zhi 16:159-63. 2008..Disruption of Smad4 gene specifically in osteoblasts leads to a remarkable decrease of osteoblast number and endosteal surface area...
- Hey1 basic helix-loop-helix protein plays an important role in mediating BMP9-induced osteogenic differentiation of mesenchymal progenitor cellsKatie A Sharff
Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois 60637, USA
J Biol Chem 284:649-59. 2009..Thus, our findings suggest that Hey1, through its interplay with Runx2, may play an important role in regulating BMP9-induced osteoblast lineage differentiation of MSCs...
- Disruption of Smad4 in odontoblasts causes multiple keratocystic odontogenic tumors and tooth malformation in miceYuanrong Gao
Genetic Laboratory of Development and Diseases, State Key Laboratory of Proteomics, Institute of Biotechnology, Beijing 100071, People s Republic of China
Mol Cell Biol 29:5941-51. 2009..Here, we show that specific ablation of Smad4 in odontoblasts unexpectedly resulted in spontaneous KCOTs in mice...
- Smad4-dependent pathways control basement membrane deposition and endodermal cell migration at early stages of mouse developmentIta Costello
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
BMC Dev Biol 9:54. 2009b>Smad4 mutant embryos arrest shortly after implantation and display a characteristic shortened proximodistal axis, a significantly reduced epiblast, as well as a thickened visceral endoderm layer...
- Smad4-Shh-Nfic signaling cascade-mediated epithelial-mesenchymal interaction is crucial in regulating tooth root developmentXiaofeng Huang
Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA
J Bone Miner Res 25:1167-78. 2010..In this study we investigated the signaling mechanism of Smad4, the common Smad for TGF-beta/BMP signaling, in HERS in regulating root development...
- Signaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampusHelena Mira
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Cell Stem Cell 7:78-89. 2010..selective ablation of Bmpr1a in hippocampal NSCs, or inactivation of BMP canonical signaling in conditional Smad4 knockout mice, transiently enhances proliferation but later leads to a reduced number of precursors, thereby ..
- Deletion of Smad4 in fibroblasts leads to defective chondrocyte maturation and cartilage production in a TGFβ type II receptor independent mannerYingqi Teng
Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Biochem Biophys Res Commun 407:633-9. 2011..b>Smad4 serves as an exclusive co-activating smad that elicits most of the transcription responses invoked by the TGFβ ..
- SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesisJingyuan Li
Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA
Development 138:1977-89. 2011..The functional significance of SMAD4, the common mediator of TGFβ/BMP signaling, in regulating the fate of CNC cells remains unclear...
- Going mad with SmadsS Zhou
Johns Hopkins Oncology Center, Baltimore, MD 21231, USA
N Engl J Med 341:1144-6. 1999
- cDNA cloning and chromosomal mapping of rat Smad2 and Smad4 and their expression in cultured rat articular chondrocytesM Osaki
Department of Orthopaedic Surgery, Nagasaki University School of Medicine, Japan
Endocr J 46:695-701. 1999..We report here the entire sequences of rat Smad2 and Smad4 which have not been identified yet...
- Immunohistochemical expression of Smads 1-6 in the 15-day gestation mouse embryo: signaling by BMPs and TGF-betasK C Flanders
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892 5055, USA
Dev Dyn 220:141-54. 2001..Smads 1, 5, and 8 transmit signals from BMPs, while Smads 2 and 3 transmit signals from TGF-betas and activin. Smad 4 is a common mediator of both pathways, while Smads 6 and 7 inhibit signaling...
- SNO GENE FUNCTION IN GROWTH AND DEVELOPMENTSonia Pearson White; Fiscal Year: 2002..These studies will establish the contribution of the Ski/Sno gene family to the genetic regulation of development in the embryo. Health-related benefits include possible insights into hemolymphopoietic cell function and birth defects. ..
- Parenchymal/Stem Cell Pathways for Salivary Gland RepairRobert Redman; Fiscal Year: 2003..abstract_text> ..
- Identification of extrinsic signals in blood formationJan Christian; Fiscal Year: 2006..Understanding how normal blood development occurs is crucial to understanding and preventing disease resulting from misregulation of these pathways. ..
- Analysis of BMP-4 activity in Cleavage mutant miceJan Christian; Fiscal Year: 2007..Understanding the molecular mechanisms by which BMP activity is regulated is key to understanding, treating and preventing congenital anomalies and diseases. [unreadable] [unreadable]..
- A Screen for Mouse Cardiovascular Morphogenesis MutantsIvan Moskowitz; Fiscal Year: 2008..The candidate will combine clinical expertise with research training to pursue a career as a clinician-scientist in the field of cardiovascular morphogenesis and congenital heart disease. ..
- Nucleocytoplasmic Trafficking of SmadsLan Xu; Fiscal Year: 2008..These regulators of subcellular localization potential targets for therapeutic interventions aimed at modulating TGF-beta signaling diseases such as cancer. ..