Bcl 2

Summary

Gene Symbol: Bcl 2
Description: BCL2, apoptosis regulator
Alias: Bcl-2, PPP1R50, apoptosis regulator Bcl-2, B-cell CLL/lymphoma 2, protein phosphatase 1, regulatory subunit 50
Species: human
Products:     Bcl 2

Top Publications

  1. Koh Y, Park C, Yoon D, Suh C, Huh J. Prognostic significance of COX-2 expression and correlation with Bcl-2 and VEGF expression, microvessel density, and clinical variables in classical Hodgkin lymphoma. Am J Surg Pathol. 2013;37:1242-51 pubmed publisher
    ..013). COX-2 and VEGF correlated with angiogenesis and tumor progression in cHL. The findings support targeting COX-2 as a potential new therapeutic approach in cHL. ..
  2. Berndt S, Skibola C, Joseph V, Camp N, Nieters A, Wang Z, et al. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. Nat Genet. 2013;45:868-76 pubmed publisher
    ..3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism. ..
  3. Heubner M, Wimberger P, Otterbach F, Kasimir Bauer S, Siffert W, Kimmig R, et al. Association of the AA genotype of the BCL2 (-938C>A) promoter polymorphism with better survival in ovarian cancer. Int J Biol Markers. 2009;24:223-9 pubmed
    ..Recently, a novel regulatory single nucleotide polymorphism (-938C>A) in the inhibitory P2 BCL2 promoter was described. In this study we investigated its potential association with survival in epithelial ovarian cancer...
  4. Guo S, Zhi Y, Yang H, Yu Y, Wang Y, Zhang J, et al. Bcl-2 expression is associated with poor prognosis of solitary plasmacytoma of bone. Ann Hematol. 2014;93:471-7 pubmed publisher
    ..In conclusion, results showed Bcl-2 expression to be a clinically significant prognostic indicator for SPB patients and constitutive activated STAT3 may not be the sole primary regulatory mechanism. ..
  5. Lamy L, Ngo V, Emre N, Shaffer A, Yang Y, Tian E, et al. Control of autophagic cell death by caspase-10 in multiple myeloma. Cancer Cell. 2013;23:435-49 pubmed publisher
    ..While myeloma cells require a basal level of autophagy for survival, caspase-10 tempers this response to avoid cell death. Drugs that disrupt this vital balance may have therapeutic potential in myeloma. ..
  6. Vaillant F, Merino D, Lee L, Breslin K, Pal B, Ritchie M, et al. Targeting BCL-2 with the BH3 mimetic ABT-199 in estrogen receptor-positive breast cancer. Cancer Cell. 2013;24:120-9 pubmed publisher
    ..Importantly, these two classes of inhibitor further enhanced tumor response in combination therapy with tamoxifen. Collectively, our findings provide a rationale for the clinical evaluation of BH3 mimetics in therapy for breast cancer. ..
  7. Lin J, Wu Y, Yang D, Zhao Y. Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo. Oncol Rep. 2013;30:731-8 pubmed publisher
    ....
  8. Narita M, Shimizu S, Ito T, Chittenden T, Lutz R, Matsuda H, et al. Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc Natl Acad Sci U S A. 1998;95:14681-6 pubmed
    ..Taken together, these findings suggest that proapoptotic Bcl-2 family proteins, including Bax and Bak, induce the mitochondrial PT and cytochrome c release by interacting with the PT pores. ..
  9. Mohammad R, Wang S, Aboukameel A, Chen B, Wu X, Chen J, et al. Preclinical studies of a nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-X(L) [(-)-gossypol] against diffuse large cell lymphoma. Mol Cancer Ther. 2005;4:13-21 pubmed
    ..We conclude that adding Bcl-2/Bcl-X(L) small-molecule inhibitor to standard chemotherapy may prove an effective strategy in lymphoma therapy. ..
  10. Choi H, Han J. Overexpression of phospholipase D enhances Bcl-2 expression by activating STAT3 through independent activation of ERK and p38MAPK in HeLa cells. Biochim Biophys Acta. 2012;1823:1082-91 pubmed publisher
    ....

Detail Information

Publications62

  1. Koh Y, Park C, Yoon D, Suh C, Huh J. Prognostic significance of COX-2 expression and correlation with Bcl-2 and VEGF expression, microvessel density, and clinical variables in classical Hodgkin lymphoma. Am J Surg Pathol. 2013;37:1242-51 pubmed publisher
    ..013). COX-2 and VEGF correlated with angiogenesis and tumor progression in cHL. The findings support targeting COX-2 as a potential new therapeutic approach in cHL. ..
  2. Berndt S, Skibola C, Joseph V, Camp N, Nieters A, Wang Z, et al. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. Nat Genet. 2013;45:868-76 pubmed publisher
    ..3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism. ..
  3. Heubner M, Wimberger P, Otterbach F, Kasimir Bauer S, Siffert W, Kimmig R, et al. Association of the AA genotype of the BCL2 (-938C>A) promoter polymorphism with better survival in ovarian cancer. Int J Biol Markers. 2009;24:223-9 pubmed
    ..Recently, a novel regulatory single nucleotide polymorphism (-938C>A) in the inhibitory P2 BCL2 promoter was described. In this study we investigated its potential association with survival in epithelial ovarian cancer...
  4. Guo S, Zhi Y, Yang H, Yu Y, Wang Y, Zhang J, et al. Bcl-2 expression is associated with poor prognosis of solitary plasmacytoma of bone. Ann Hematol. 2014;93:471-7 pubmed publisher
    ..In conclusion, results showed Bcl-2 expression to be a clinically significant prognostic indicator for SPB patients and constitutive activated STAT3 may not be the sole primary regulatory mechanism. ..
  5. Lamy L, Ngo V, Emre N, Shaffer A, Yang Y, Tian E, et al. Control of autophagic cell death by caspase-10 in multiple myeloma. Cancer Cell. 2013;23:435-49 pubmed publisher
    ..While myeloma cells require a basal level of autophagy for survival, caspase-10 tempers this response to avoid cell death. Drugs that disrupt this vital balance may have therapeutic potential in myeloma. ..
  6. Vaillant F, Merino D, Lee L, Breslin K, Pal B, Ritchie M, et al. Targeting BCL-2 with the BH3 mimetic ABT-199 in estrogen receptor-positive breast cancer. Cancer Cell. 2013;24:120-9 pubmed publisher
    ..Importantly, these two classes of inhibitor further enhanced tumor response in combination therapy with tamoxifen. Collectively, our findings provide a rationale for the clinical evaluation of BH3 mimetics in therapy for breast cancer. ..
  7. Lin J, Wu Y, Yang D, Zhao Y. Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo. Oncol Rep. 2013;30:731-8 pubmed publisher
    ....
  8. Narita M, Shimizu S, Ito T, Chittenden T, Lutz R, Matsuda H, et al. Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc Natl Acad Sci U S A. 1998;95:14681-6 pubmed
    ..Taken together, these findings suggest that proapoptotic Bcl-2 family proteins, including Bax and Bak, induce the mitochondrial PT and cytochrome c release by interacting with the PT pores. ..
  9. Mohammad R, Wang S, Aboukameel A, Chen B, Wu X, Chen J, et al. Preclinical studies of a nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-X(L) [(-)-gossypol] against diffuse large cell lymphoma. Mol Cancer Ther. 2005;4:13-21 pubmed
    ..We conclude that adding Bcl-2/Bcl-X(L) small-molecule inhibitor to standard chemotherapy may prove an effective strategy in lymphoma therapy. ..
  10. Choi H, Han J. Overexpression of phospholipase D enhances Bcl-2 expression by activating STAT3 through independent activation of ERK and p38MAPK in HeLa cells. Biochim Biophys Acta. 2012;1823:1082-91 pubmed publisher
    ....
  11. Schurmann A, Mooney A, Sanders L, Sells M, Wang H, Reed J, et al. p21-activated kinase 1 phosphorylates the death agonist bad and protects cells from apoptosis. Mol Cell Biol. 2000;20:453-61 pubmed
    ..Our findings indicate that PAK inhibits the proapoptotic effects of Bad by direct phosphorylation and that PAK may play an important role in cell survival pathways. ..
  12. Chen L, Willis S, Wei A, Smith B, Fletcher J, Hinds M, et al. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell. 2005;17:393-403 pubmed
    ..The results suggest that apoptosis relies on selective interactions between particular subsets of these proteins and that it should be feasible to discover BH3-mimetic drugs that inactivate specific prosurvival targets. ..
  13. Hussein M. Analysis of p53, BCL-2 and epidermal growth factor receptor protein expression in the partial and complete hydatidiform moles. Exp Mol Pathol. 2009;87:63-9 pubmed publisher
    ..The lack of significant p53 protein overexpression suggests the lack of underlying p53 mutations in hydatidiform moles. ..
  14. Wang H, Rapp U, Reed J. Bcl-2 targets the protein kinase Raf-1 to mitochondria. Cell. 1996;87:629-38 pubmed
    ..Bcl-2 can therefore target Raf-1 to mitochondrial membranes, allowing this kinase to phosphorylate BAD or possibly other protein substrates involved in apoptosis regulation. ..
  15. Shibasaki F, Kondo E, Akagi T, McKeon F. Suppression of signalling through transcription factor NF-AT by interactions between calcineurin and Bcl-2. Nature. 1997;386:728-31 pubmed
    ..We propose that the ability of Bcl-2 to block NF-AT signalling is due to the sequestering of active calcineurin to the same domain of Bcl-2 which associates with Rad-1 (ref. 5), and that calcineurin may act in Bcl-2-regulated functions. ..
  16. Edlich F, Banerjee S, Suzuki M, Cleland M, Arnoult D, Wang C, et al. Bcl-x(L) retrotranslocates Bax from the mitochondria into the cytosol. Cell. 2011;145:104-16 pubmed publisher
    ..We propose that Bcl-x(L) inhibits and maintains Bax in the cytosol by constant retrotranslocation of mitochondrial Bax. ..
  17. Yang E, Zha J, Jockel J, Boise L, Thompson C, Korsmeyer S. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell. 1995;80:285-91 pubmed
    ..The susceptibility of a cell to a death signal is determined by these competing dimerizations in which levels of Bad influence the effectiveness of Bcl-2 versus Bcl-xL in repressing death. ..
  18. Moon J, Sohn S, Lee M, Jang J, Kim K, Jung C, et al. BCL2 gene polymorphism could predict the treatment outcomes in acute myeloid leukemia patients. Leuk Res. 2010;34:166-72 pubmed publisher
    ..05, HR 1.83, 95% C.I. [1.02-3.45]) and EFS (p=0.02, HR 3.13 [1.34-6.43]), but not for OS (p=0.1). This data suggests the involvement of a Bcl-2-mediated mechanism in the development of chemoresistance in AML. ..
  19. Zha J, Harada H, Osipov K, Jockel J, Waksman G, Korsmeyer S. BH3 domain of BAD is required for heterodimerization with BCL-XL and pro-apoptotic activity. J Biol Chem. 1997;272:24101-4 pubmed
    ..These results establish a critical role for a BH3 domain within BAD and provide evidence that BAD may function as a death ligand whose pro-apoptotic activity requires heterodimerization with BCL-XL. ..
  20. Azad N, Vallyathan V, Wang L, Tantishaiyakul V, Stehlik C, Leonard S, et al. S-nitrosylation of Bcl-2 inhibits its ubiquitin-proteasomal degradation. A novel antiapoptotic mechanism that suppresses apoptosis. J Biol Chem. 2006;281:34124-34 pubmed
    ..These findings indicate a novel function of NO and its regulation of Bcl-2, which provides a key mechanism for the control of apoptotic cell death and cancer development...
  21. Jin Z, May W, Gao F, Flagg T, Deng X. Bcl2 suppresses DNA repair by enhancing c-Myc transcriptional activity. J Biol Chem. 2006;281:14446-56 pubmed
    ..Thus, Bcl2, in addition to its survival function, may also suppress DNA repair in a novel mechanism involving c-Myc and APE1, which may lead to an accumulation of DNA damage in living cells, genetic instability, and tumorigenesis. ..
  22. Zauli G, Gibellini D, Milani D, Mazzoni M, Borgatti P, La Placa M, et al. Human immunodeficiency virus type 1 Tat protein protects lymphoid, epithelial, and neuronal cell lines from death by apoptosis. Cancer Res. 1993;53:4481-5 pubmed
    ....
  23. Zhai D, Jin C, Huang Z, Satterthwait A, Reed J. Differential regulation of Bax and Bak by anti-apoptotic Bcl-2 family proteins Bcl-B and Mcl-1. J Biol Chem. 2008;283:9580-6 pubmed publisher
    ..Altogether, the findings reveal striking distinctions in the behaviors of Bcl-B and Mcl-1 relative to the other anti-apoptotic Bcl-2 family members, where Bcl-B and Mcl-1 display reciprocal abilities to bind and neutralize Bax and Bak. ..
  24. Bredow S, Juri D, Cardon K, Tesfaigzi Y. Identification of a novel Bcl-2 promoter region that counteracts in a p53-dependent manner the inhibitory P2 region. Gene. 2007;404:110-6 pubmed
    ..These findings may have implications for therapies that are geared towards inhibiting bcl-2 gene expression and inducing cell death. ..
  25. Huang S, Cidlowski J. Phosphorylation status modulates Bcl-2 function during glucocorticoid-induced apoptosis in T lymphocytes. FASEB J. 2002;16:825-32 pubmed
    ..Mutation of T74 only partially impaired the ability of Bcl-2 to block glucocorticoid-induced apoptosis whereas mutation of S70 in Bcl-2 did not alter its ability to block glucocorticoid-induced apoptosis. ..
  26. Maiuri M, Criollo A, Tasdemir E, Vicencio J, Tajeddine N, Hickman J, et al. BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-X(L). Autophagy. 2007;3:374-6 pubmed
    ..On the other hand, they can activate autophagy by liberating Beclin 1 from its inhibition by Bcl-2/Bcl-X(L) at the level of the endoplasmic reticulum. ..
  27. Breitschopf K, Haendeler J, Malchow P, Zeiher A, Dimmeler S. Posttranslational modification of Bcl-2 facilitates its proteasome-dependent degradation: molecular characterization of the involved signaling pathway. Mol Cell Biol. 2000;20:1886-96 pubmed
    ..Taken together, these results demonstrate a direct protective role for Bcl-2 phosphorylation by MAP kinase against apoptotic challenges to endothelial cells and other cells. ..
  28. Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, et al. p53 has a direct apoptogenic role at the mitochondria. Mol Cell. 2003;11:577-90 pubmed
    ..This opens the possibility that mutations might represent "double-hits" by abrogating the transcriptional and mitochondrial apoptotic activity of p53. ..
  29. Boiani M, Daniel C, Liu X, Hogarty M, Marnett L. The stress protein BAG3 stabilizes Mcl-1 protein and promotes survival of cancer cells and resistance to antagonist ABT-737. J Biol Chem. 2013;288:6980-90 pubmed publisher
    ..These studies identify BAG3-mediated Mcl-1 stabilization as a potential target for cancer drug discovery. ..
  30. Gregoire I, Richetta C, Meyniel Schicklin L, Borel S, Pradezynski F, Diaz O, et al. IRGM is a common target of RNA viruses that subvert the autophagy network. PLoS Pathog. 2011;7:e1002422 pubmed publisher
    ..Our work reveals an unexpected role of IRGM in virus-induced autophagy and suggests that several different families of RNA viruses may use common strategies to manipulate autophagy to improve viral infectivity. ..
  31. Criollo A, Senovilla L, Authier H, Maiuri M, Morselli E, Vitale I, et al. The IKK complex contributes to the induction of autophagy. EMBO J. 2010;29:619-31 pubmed publisher
    ..Altogether, these results indicate that IKK has a cardinal role in the stimulation of autophagy by physiological and pharmacological stimuli. ..
  32. Kang R, Tang D, Yu Y, Wang Z, Hu T, Wang H, et al. WAVE1 regulates Bcl-2 localization and phosphorylation in leukemia cells. Leukemia. 2010;24:177-86 pubmed publisher
    ..Taken together, these results suggest WAVE1 as a novel regulator of apoptosis, and potential drug target for therapeutic intervention of leukemia. ..
  33. Jacotot E, Ravagnan L, Loeffler M, Ferri K, Vieira H, Zamzami N, et al. The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore. J Exp Med. 2000;191:33-46 pubmed
    ..Hence, Vpr induces apoptosis via a direct effect on the mitochondrial PTPC. ..
  34. Naumovski L, Cleary M. The p53-binding protein 53BP2 also interacts with Bc12 and impedes cell cycle progression at G2/M. Mol Cell Biol. 1996;16:3884-92 pubmed
    ..The in vivo significance of these interactions and their potential consequences for cell cycle progression and cell death remain to be determined. ..
  35. Fernandez Sarabia M, Bischoff J. Bcl-2 associates with the ras-related protein R-ras p23. Nature. 1993;366:274-5 pubmed
    ..These results provide evidence of a putative component of a signal transduction pathway involved in the regulation of apoptosis. ..
  36. Iqbal J, Meyer P, Smith L, Johnson N, Vose J, Greiner T, et al. BCL2 predicts survival in germinal center B-cell-like diffuse large B-cell lymphoma treated with CHOP-like therapy and rituximab. Clin Cancer Res. 2011;17:7785-95 pubmed publisher
    ..However, after the inclusion of rituximab (R) in the CHOP regimen, several conflicting observations about the prognostic value of BCL2 expression have been reported...
  37. Lapucci A, Donnini M, Papucci L, Witort E, Tempestini A, Bevilacqua A, et al. AUF1 Is a bcl-2 A + U-rich element-binding protein involved in bcl-2 mRNA destabilization during apoptosis. J Biol Chem. 2002;277:16139-46 pubmed
    ..Inhibition of apoptosis by a general caspase inhibitor reduces this increase by 2-3-fold. These results indicate involvement of AUF1 in the ARE/AUBP-mediated modulation of bcl-2 mRNA decay during apoptosis. ..