Genomes and Genes
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
Products: Bcl 2
- 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. ..
- 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. ..
- 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...
- 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. ..
- 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. ..
- 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. ..
- 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....
- 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. ..
- 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. ..
- 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....
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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...
- 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. ..
- 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....
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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...
- 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. ..