Bcl 2


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. Kaufmann T, Schlipf S, Sanz J, Neubert K, Stein R, Borner C. Characterization of the signal that directs Bcl-x(L), but not Bcl-2, to the mitochondrial outer membrane. J Cell Biol. 2003;160:53-64 pubmed
    ..These data define a new targeting sequence for the MOM and propose that Bcl-2 acts on several intracellular membranes whereas Bcl-x(L) specifically functions on the MOM. ..
  2. Machado Vieira R, Pivovarova N, Stanika R, Yuan P, Wang Y, Zhou R, et al. The Bcl-2 gene polymorphism rs956572AA increases inositol 1,4,5-trisphosphate receptor-mediated endoplasmic reticulum calcium release in subjects with bipolar disorder. Biol Psychiatry. 2011;69:344-52 pubmed publisher
    ..These results demonstrate that, in patients with BPD, abnormal Bcl-2 gene expression in the AA variant contributes to dysfunctional Ca(2+) homeostasis through a specific ER inositol 1,4,5-trisphosphate receptor-dependent mechanism. ..
  3. Johnson N, Slack G, Savage K, Connors J, Ben Neriah S, Rogic S, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30:3452-9 pubmed
    ..Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis. ..
  4. 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. ..
  5. Salvadore G, Nugent A, Chen G, Akula N, Yuan P, Cannon D, et al. Bcl-2 polymorphism influences gray matter volume in the ventral striatum in healthy humans. Biol Psychiatry. 2009;66:804-7 pubmed publisher
    ..Thus, the findings from the current study are noteworthy insofar as they converge with preclinical findings that Bcl-2 functions to enhance neuronal viability and might indirectly extend this evidence to humans. ..
  6. 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...
  7. 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. ..
  8. 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. ..
  9. Renault T, Chipuk J. Getting away with murder: how does the BCL-2 family of proteins kill with immunity?. Ann N Y Acad Sci. 2013;1285:59-79 pubmed publisher
    ..From lethal mechanisms to more gentle ones, the final portion of the review discusses the nonapoptotic functions of the BCL-2 family and how they pertain to the control of immunity. ..

More Information

Publications196 found, 100 shown here

  1. 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. ..
  2. 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. ..
  3. 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. ..
  4. Geng M, Wang L, Li P. Correlation between chemosensitivity to anticancer drugs and Bcl-2 expression in gastric cancer. Int J Clin Exp Pathol. 2013;6:2554-9 pubmed
    ..009). Overexpression of Bcl-2 may predict a loss of the efficacy of the chemotherapy drugs 5-FU, ADM and MMC in patients with gastric cancer. ..
  5. Hu S, Xu Monette Z, Tzankov A, Green T, Wu L, Balasubramanyam A, et al. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Pro. Blood. 2013;121:4021-31; quiz 4250 pubmed publisher
    ..In conclusion, the data suggest that MYC/BCL2 coexpression, rather than cell-of-origin classification, is a better predictor of prognosis in patients with DLBCL treated with R-CHOP. ..
  6. 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
  7. Snuderl M, Kolman O, Chen Y, Hsu J, Ackerman A, Dal Cin P, et al. B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements are aggressive neoplasms with clinical and pathologic features distinct from Burkitt lymphoma and diffuse large B-cell lymphoma. Am J Surg Pathol. 2010;34:327-40 pubmed publisher
    ..The aggressive clinical behavior and combination of genetic abnormalities seen in these cases may warrant categorization as a separate entity in future classifications and call for novel therapeutic approaches. ..
  8. Yang Q, Moran M, Haffty B. Bcl-2 expression predicts local relapse for early-stage breast cancer receiving conserving surgery and radiotherapy. Breast Cancer Res Treat. 2009;115:343-8 pubmed publisher
    ..Immunohistochemical staining of the primary tumor for Bcl-2 might be useful to select optimal treatment options for these patients. ..
  9. Nadler Y, Camp R, Giltnane J, Moeder C, Rimm D, Kluger H, et al. Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer. Breast Cancer Res. 2008;10:R35 pubmed publisher
  10. Hockenbery D, Nunez G, Milliman C, Schreiber R, Korsmeyer S. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990;348:334-6 pubmed
    ..Thus, Bcl-2 is unique among proto-oncogenes, being localized to mitochondria and interfering with programmed cell death independent of promoting cell division. ..
  11. Reshmi G, Surya R, Jissa V, Babu P, Preethi N, Santhi W, et al. C-T variant in a miRNA target site of BCL2 is associated with increased risk of human papilloma virus related cervical cancer--an in silico approach. Genomics. 2011;98:189-93 pubmed publisher
    ..The results also paves way for future studies to validate these results in other well-characterized populations as well as to explore the biological significance of these particular SNPs. ..
  12. Visco C, Tzankov A, Xu Monette Z, Miranda R, Tai Y, Li Y, et al. Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP Consortium Program Study. Haematologica. 2013;98:255-63 pubmed publisher
    ..BCL2 translocated germinal center subtype patients have worse prognosis after rituximab-CHOP, irrespective of MYC status, but the presence of combined gene breaks significantly overcomes the prognostic relevance of isolated lesions. ..
  13. Larramendy M, Niini T, Elonen E, Nagy B, Ollila J, Vihinen M, et al. Overexpression of translocation-associated fusion genes of FGFRI, MYC, NPMI, and DEK, but absence of the translocations in acute myeloid leukemia. A microarray analysis. Haematologica. 2002;87:569-77 pubmed
    ..Clinical and prognostic significance of differential gene expression should be studied with a larger series of patients by using other techniques, such as quantitative real-time PCR. ..
  14. Moon D, Kim M, Choi Y, Kim N, Chang J, Kim G. Bcl-2 overexpression attenuates SP600125-induced apoptosis in human leukemia U937 cells. Cancer Lett. 2008;264:316-25 pubmed publisher
    ..These data provide important mechanistic insights related to Bcl-2-mediated resistance to SP600125-induced apoptosis, and induction of G2/M phase arrest and endoreduplication. ..
  15. Thomenius M, Wang N, Reineks E, Wang Z, Distelhorst C. Bcl-2 on the endoplasmic reticulum regulates Bax activity by binding to BH3-only proteins. J Biol Chem. 2003;278:6243-50 pubmed
    ..These data suggest that Bcl-2 indirectly protects mitochondrial membranes from Bax, via BH3-only proteins. ..
  16. Dominov J, Kravetz A, Ardelt M, Kostek C, Beermann M, Miller J. Muscle-specific BCL2 expression ameliorates muscle disease in laminin {alpha}2-deficient, but not in dystrophin-deficient, mice. Hum Mol Genet. 2005;14:1029-40 pubmed
  17. Puthalakath H, Villunger A, O Reilly L, Beaumont J, Coultas L, Cheney R, et al. Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. Science. 2001;293:1829-32 pubmed
    ..Thus, at least two mammalian BH3-only proteins, Bmf and Bim, function to sense intracellular damage by their localization to distinct cytoskeletal structures. ..
  18. Muthumani K, Hwang D, Desai B, Zhang D, Dayes N, Green D, et al. HIV-1 Vpr induces apoptosis through caspase 9 in T cells and peripheral blood mononuclear cells. J Biol Chem. 2002;277:37820-31 pubmed
    ..Bcl-2 overexpressing cells succumb to Vpr-induced apoptosis. These studies illustrate that Vpr induces a mitochondria-dependent apoptotic pathway that is distinct from apoptosis driven by the Fas-FasL pathway. ..
  19. Certo M, Del Gaizo Moore V, Nishino M, Wei G, Korsmeyer S, Armstrong S, et al. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell. 2006;9:351-65 pubmed
    ..Our data allow us to distinguish a cellular state we call "primed for death," which can be determined by BH3 profiling and which correlates with dependence on antiapoptotic family members for survival. ..
  20. Ruvolo P, Deng X, May W. Phosphorylation of Bcl2 and regulation of apoptosis. Leukemia. 2001;15:515-22 pubmed
    ..While post-translational mechanisms other than phosphorylation may also regulate Bcl2's function (eg ubiquitination), this review will focus on the regulatory role for phosphorylation and discuss its potential clinical ramifications. ..
  21. Tawfik K, Kimler B, Davis M, Fan F, Tawfik O. Prognostic significance of Bcl-2 in invasive mammary carcinomas: a comparative clinicopathologic study between "triple-negative" and non-"triple-negative" tumors. Hum Pathol. 2012;43:23-30 pubmed publisher
    ..Our results establish the value of using Bcl-2 in prognostic stratification of patients and its potential therapeutic implications in selecting patients for treatment. ..
  22. Garg H, Mohl J, Joshi A. HIV-1 induced bystander apoptosis. Viruses. 2012;4:3020-43 pubmed publisher
  23. Callagy G, Webber M, Pharoah P, Caldas C. Meta-analysis confirms BCL2 is an independent prognostic marker in breast cancer. BMC Cancer. 2008;8:153 pubmed publisher
    ..Large prospective studies are now needed to establish the clinical utility of BCL2 as an independent prognostic marker. ..
  24. Yamamoto K, Ichijo H, Korsmeyer S. BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol. 1999;19:8469-78 pubmed
    ..Thus, stress response kinases phosphorylate BCL-2 during cell cycle progression as a normal physiologic process to inactivate BCL-2 at G(2)/M. ..
  25. Deng X, Ruvolo P, Carr B, May W. Survival function of ERK1/2 as IL-3-activated, staurosporine-resistant Bcl2 kinases. Proc Natl Acad Sci U S A. 2000;97:1578-83 pubmed
    ..In addition, although the mechanism of regulation of Bcl2 by phosphorylation is not yet clear, our results indicate that phosphorylation may functionally stabilize the Bcl2-Bax heterodimerization. ..
  26. Pathan N, Aime Sempe C, Kitada S, Basu A, Haldar S, Reed J. Microtubule-targeting drugs induce bcl-2 phosphorylation and association with Pin1. Neoplasia. 2001;3:550-9 pubmed
  27. Sun Q, Fan W, Chen K, Ding X, Chen S, Zhong Q. Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase. Proc Natl Acad Sci U S A. 2008;105:19211-6 pubmed publisher
  28. Samuels Lev Y, O Connor D, Bergamaschi D, Trigiante G, Hsieh J, Zhong S, et al. ASPP proteins specifically stimulate the apoptotic function of p53. Mol Cell. 2001;8:781-94 pubmed
    ..The expression of ASPP is frequently downregulated in human breast carcinomas expressing wild-type p53 but not mutant p53. Therefore, ASPP regulate the tumor suppression function of p53 in vivo. ..
  29. Uemura T, Green M, Corson T, Perova T, Li P, Warsh J. Bcl-2 SNP rs956572 associates with disrupted intracellular calcium homeostasis in bipolar I disorder. Bipolar Disord. 2011;13:41-51 pubmed publisher
    ..These findings support the notion that genetic variation in Bcl-2 affecting its expression impacts ICH in BD. Moreover, we show here for the first time that this interactive effect is diagnostically specific to BD-I. ..
  30. Hoetelmans R. Nuclear partners of Bcl-2: Bax and PML. DNA Cell Biol. 2004;23:351-4 pubmed
    ..These data show that binding of Bcl-2 with structurally and functionally related proteins extends to the nucleus, emphasizing its pivotal role in Bcl-2-mediated actions. ..
  31. Horn H, Ziepert M, Becher C, Barth T, Bernd H, Feller A, et al. MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma. Blood. 2013;121:2253-63 pubmed publisher
    ..Registered at http://www.cancer.gov/clinicaltrials: RICOVER trial of the DSHNHL is NCT 00052936. ..
  32. Heckman C, Mehew J, Boxer L. NF-kappaB activates Bcl-2 expression in t(14;18) lymphoma cells. Oncogene. 2002;21:3898-908 pubmed
    ..We therefore conclude that the activation of bcl-2 by NF-kappaB in t(14;18) lymphoma cells is mediated through the CRE and Sp1 binding sites. ..
  33. Reed J, Zha H, Aime Sempe C, Takayama S, Wang H. Structure-function analysis of Bcl-2 family proteins. Regulators of programmed cell death. Adv Exp Med Biol. 1996;406:99-112 pubmed
    ..Further studies however are required to delineate the full significance of Bcl-2/Bcl-2, Bcl-2/Bax, and Bax/Bax dimers and the biochemical mechanisms by which Bcl-2 family proteins ultimately control cell life and death. ..
  34. Maiuri M, Le Toumelin G, Criollo A, Rain J, Gautier F, Juin P, et al. Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J. 2007;26:2527-39 pubmed
    ..BH3-only proteins and pharmacological BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin-1 and Bcl-2 or Bcl-X(L). ..
  35. Barboule N, Demeter K, Benmeradi N, Larminat F. Bcl-2 is an integral component of mitotic chromosomes. Cell Biol Int. 2009;33:572-7 pubmed publisher
    ..Bcl-2 localization at the periphery and over the mitotic chromosome was confirmed by immunoelectron microscopy on mitotic cells. Our results indicate that Bcl-2 is an integral component of the mitotic chromosome...
  36. Ishimaru D, Ramalingam S, Sengupta T, Bandyopadhyay S, Dellis S, Tholanikunnel B, et al. Regulation of Bcl-2 expression by HuR in HL60 leukemia cells and A431 carcinoma cells. Mol Cancer Res. 2009;7:1354-66 pubmed publisher
    ..HuR knockdown also leads to redistribution of bcl-2 mRNA from polysomes to monosomes. Thus, HuR seems to play a positive role in both regulation of bcl-2 mRNA translation and mRNA stability. ..
  37. Ha J, Shin J, Yoon M, Lee M, He F, Bae K, et al. Dual-site interactions of p53 protein transactivation domain with anti-apoptotic Bcl-2 family proteins reveal a highly convergent mechanism of divergent p53 pathways. J Biol Chem. 2013;288:7387-98 pubmed publisher
    ..In conclusion, our results suggest that the dual-site interaction of p53TAD is a highly conserved mechanism underlying target protein binding in the transcription-dependent and transcription-independent apoptotic pathways of p53. ..
  38. Krajewski S, Tanaka S, Takayama S, Schibler M, Fenton W, Reed J. Investigation of the subcellular distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes. Cancer Res. 1993;53:4701-14 pubmed
  39. Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, et al. Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science. 2000;288:1053-8 pubmed
    ..We also demonstrate that blocking the endogenous Noxa induction results in the suppression of apoptosis. Noxa may thus represent a mediator of p53-dependent apoptosis. ..
  40. Cory S, Adams J. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2:647-56 pubmed
    ..Apoptosis is often impaired in cancer and can limit conventional therapy. A better understanding of how the Bcl2 family controls caspase activation should result in new, more effective therapeutic approaches. ..
  41. Pasinelli P, Belford M, Lennon N, Bacskai B, Hyman B, Trotti D, et al. Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria. Neuron. 2004;43:19-30 pubmed
    ..These findings provide new insights into the anti-apoptotic function of SOD1 and suggest that entrapment of Bcl-2 by large SOD1 aggregates may deplete motor neurons of this anti-apoptotic protein. ..
  42. Kuo T, Kim H, Zhu L, Yu Y, Lin H, Tsang W. Modulation of endoplasmic reticulum calcium pump by Bcl-2. Oncogene. 1998;17:1903-10 pubmed
    ..Since high lumenal Ca2+ concentration of ER is essential for normal cell functions, the results suggest that Bcl-2 preserves the ER Ca2+ store by upregulating SERCA gene expression as well as by a possible interaction with the pump. ..
  43. Gallenne T, Gautier F, Oliver L, Hervouet E, Noël B, Hickman J, et al. Bax activation by the BH3-only protein Puma promotes cell dependence on antiapoptotic Bcl-2 family members. J Cell Biol. 2009;185:279-90 pubmed publisher
    ..Thus, Puma is competent to trigger Bax activity by itself, thereby promoting cellular dependence on prosurvival Bcl-2 family members. ..
  44. Park Y, Sohn S, Kim J, Lee M, Song H, Kim M, et al. Interaction between BCL2 and interleukin-10 gene polymorphisms alter outcomes of diffuse large B-cell lymphoma following rituximab plus CHOP chemotherapy. Clin Cancer Res. 2009;15:2107-15 pubmed publisher
    ..004) compared with other genotype groups when treated with R-CHOP chemotherapy. These data indicated that R-CHOP chemotherapy resistance in diffuse large B-cell lymphoma may involve interactions between the BCL2 and IL10 genes. ..
  45. Rong Y, Bultynck G, Aromolaran A, Zhong F, Parys J, De Smedt H, et al. The BH4 domain of Bcl-2 inhibits ER calcium release and apoptosis by binding the regulatory and coupling domain of the IP3 receptor. Proc Natl Acad Sci U S A. 2009;106:14397-402 pubmed publisher
    ..By inhibiting proapoptotic Ca(2+) signals at their point of origin, the Bcl-2 BH4 domain has the facility to block diverse pathways through which Ca(2+) induces apoptosis. ..
  46. Zhu L, Xiang R, Dong W, Liu Y, Qi Y. Anti-apoptotic activity of Bcl-2 is enhanced by its interaction with RTN3. Cell Biol Int. 2007;31:825-30 pubmed
    ..These results suggest that RTN3 could bind with Bcl-2 and mediate its accumulation in mitochondria, which modulate the anti-apoptotic activity of Bcl-2. ..
  47. Yildirim M, Suren D, Goktas S, Dilli U, Kaya C, Copuroglu R, et al. The predictive role of Bcl-2 expression in operable locally advanced or metastatic gastric carcinoma. J BUON. 2012;17:106-9 pubmed
    ..We believe that Bcl-2 expression has an additional contribution in predicting response to this chemotherapy combination. ..
  48. Haughn L, Hawley R, Morrison D, von Boehmer H, Hockenbery D. BCL-2 and BCL-XL restrict lineage choice during hematopoietic differentiation. J Biol Chem. 2003;278:25158-65 pubmed
    ..These effects are associated with differential regulation of Raf-1 expression, perhaps involving the previously identified interaction between BCL-2-BH4 and the catalytic domain of Raf-1. ..
  49. Seto M, Jaeger U, Hockett R, Graninger W, Bennett S, Goldman P, et al. Alternative promoters and exons, somatic mutation and deregulation of the Bcl-2-Ig fusion gene in lymphoma. EMBO J. 1988;7:123-31 pubmed
    ..5 h half-life, the Bcl-2--Ig gene revealed an inappropriately high rate of transcription for a mature B-cell. This indicates the translocated Bcl-2 allele has escaped normal control mechanisms. ..
  50. Roumier T, Vieira H, Castedo M, Ferri K, Boya P, Andreau K, et al. The C-terminal moiety of HIV-1 Vpr induces cell death via a caspase-independent mitochondrial pathway. Cell Death Differ. 2002;9:1212-9 pubmed
    ..In conclusion, it appears that Vpr induces apoptosis through a caspase-independent mitochondrial pathway. ..
  51. Oltvai Z, Milliman C, Korsmeyer S. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993;74:609-19 pubmed
    ..Overexpressed Bax also counters the death repressor activity of Bcl-2. These data suggest a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus. ..
  52. Callagy G, Pharoah P, Pinder S, Hsu F, Nielsen T, Ragaz J, et al. Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham Prognostic Index. Clin Cancer Res. 2006;12:2468-75 pubmed
    ..001) with an effect that was maximal in the first 5 years. Bcl-2 is an independent predictor of breast cancer outcome and seems to be useful as a prognostic adjunct to the NPI, particularly in the first 5 years after diagnosis. ..
  53. Luo X, Budihardjo I, Zou H, Slaughter C, Wang X. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell. 1998;94:481-90 pubmed
    ..The cytochrome c releasing activity of Bid was antagonized by Bcl2. A mutation at the BH3 domain diminished its cytochrome c releasing activity. Bid, therefore, relays an apoptotic signal from the cell surface to mitochondria. ..
  54. Majid A, Tsoulakis O, Walewska R, Gesk S, Siebert R, Kennedy D, et al. BCL2 expression in chronic lymphocytic leukemia: lack of association with the BCL2 938A>C promoter single nucleotide polymorphism. Blood. 2008;111:874-7 pubmed
    ..BCL2 protein levels in CLL reflect a complex interplay of transcriptional and posttranscriptional controls, but do not appear to be associated with the -938C>A promoter SNP. ..
  55. Cimmino A, Calin G, Fabbri M, Iorio M, Ferracin M, Shimizu M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102:13944-9 pubmed
    ..BCL2 repression by these microRNAs induces apoptopsis in a leukemic cell line model. Therefore, miR-15 and miR-16 are natural antisense Bcl2 interactors that could be used for therapy of Bcl2-overexpressing tumors. ..
  56. Wan Q, Kuang E, Dong W, Zhou S, Xu H, Qi Y, et al. Reticulon 3 mediates Bcl-2 accumulation in mitochondria in response to endoplasmic reticulum stress. Apoptosis. 2007;12:319-28 pubmed
    ..Taken together, our findings indicate that RTN3 is directly involved in the ER-constituents trafficking events through dually acting as an essential and important ER-stress sensor, and a trigger for the Bcl-2 translocation. ..
  57. Rouette A, Parent S, Girouard J, Leblanc V, Asselin E. Cisplatin increases B-cell-lymphoma-2 expression via activation of protein kinase C and Akt2 in endometrial cancer cells. Int J Cancer. 2012;130:1755-67 pubmed publisher
    ..Our data suggest a novel regulation pathway of Bcl-2 by cisplatin, via the activation of PKC and Akt2, which has a profound impact on resistance to cisplatin-induced apoptosis in endometrial cancer cells. ..
  58. Sun T, Sun B, Zhao X, Zhao N, Dong X, Che N, et al. Promotion of tumor cell metastasis and vasculogenic mimicry by way of transcription coactivation by Bcl-2 and Twist1: a study of hepatocellular carcinoma. Hepatology. 2011;54:1690-706 pubmed publisher
    ..The results describe a novel function of Bcl-2 in EMT induction, provide insight into tumor progression, and implicate the Bcl-2/Twist1 complex as a potential target for developing chemotherapeutics. ..
  59. Chauhan P, Bhushan B, Singh L, Mishra A, Saluja S, Mittal V, et al. Expression of genes related to multiple drug resistance and apoptosis in acute leukemia: response to induction chemotherapy. Exp Mol Pathol. 2012;92:44-9 pubmed publisher
    ..001, p=0.02 and p=0.007 respectively). These results showed the potential clinical relevance of MDR1, MRP1 and BCL-2 in adult patients with acute leukemia in the context of induction chemotherapy. ..
  60. Wei Y, Pattingre S, Sinha S, Bassik M, Levine B. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell. 2008;30:678-88 pubmed publisher
    ..These findings define a mechanism that cells use to regulate autophagic activity in response to nutrient status. ..
  61. Knoefel L, Werle Schneider G, Dally H, Müller P, Edler L, Bartsch H, et al. Polymorphisms in the apoptotic pathway gene BCL-2 and survival in small cell lung cancer. J Thorac Oncol. 2011;6:183-9 pubmed publisher
    ..BCL-2 -938CC genotype shows significantly worse outcome in small cell lung cancer patients. This genetic marker might particularly impact on treatment strategies using BCL-2 antisense approaches. ..
  62. Gu H, Rao S, Zhao J, Wang J, Mu R, Rong J, et al. Gambogic acid reduced bcl-2 expression via p53 in human breast MCF-7 cancer cells. J Cancer Res Clin Oncol. 2009;135:1777-82 pubmed publisher
    ..Same result was observed after p53 knock-down by p53 si-RNA. Gambogic acid induced human breast cancer cells MCF-7 apoptosis by reducing bcl-2 expression via p53. ..
  63. Willis S, Chen L, Dewson G, Wei A, Naik E, Fletcher J, et al. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev. 2005;19:1294-305 pubmed
    ..The finding that different prosurvival proteins have selective roles has notable implications for the design of anti-cancer drugs that target the Bcl-2 family. ..
  64. Pattingre S, Tassa A, Qu X, Garuti R, Liang X, Mizushima N, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 2005;122:927-39 pubmed
    ..This antiautophagy function of Bcl-2 may help maintain autophagy at levels that are compatible with cell survival, rather than cell death. ..
  65. Kaderi M, Norberg M, Murray F, Merup M, Sundstrom C, Roos G, et al. The BCL-2 promoter (-938C>A) polymorphism does not predict clinical outcome in chronic lymphocytic leukemia. Leukemia. 2008;22:339-43 pubmed
    ..Taken together, our data do not support the use of the (-938C>A) BCL-2 polymorphism as a prognostic marker in CLL and argue against its postulated role in modulating Bcl-2 levels. ..
  66. Triantafyllou K, Kitsanta P, Karamanolis D, Kittas C, Ladas S. Epithelial cell turnover, p53 and bcl-2 protein expression during oncogenesis of early and advanced gastric cancer in a Western population. Dig Liver Dis. 2008;40:39-45 pubmed
    ..p53 and bcl-2 protein accumulation is more intense in gastric mucosa adjacent to advanced tumors and p53 immunoreactivity peaks in advanced carcinomas. ..
  67. Patel M, Masood A, Patel P, Chanan Khan A. Targeting the Bcl-2. Curr Opin Oncol. 2009;21:516-23 pubmed publisher
    ..Downregulation of Bcl-2 and restoration of a critical apoptotic pathway in cancer cells remains an important strategy. Novel Bcl-2 inhibitors have started to deliver the therapeutic promise of this target-specific quest. ..
  68. Ferreira A, Suriano G, Mendes N, Gomes B, Wen X, Carneiro F, et al. E-cadherin impairment increases cell survival through Notch-dependent upregulation of Bcl-2. Hum Mol Genet. 2012;21:334-43 pubmed publisher
    ..These findings highlight the possibility of new targeted therapeutical strategies for the treatment of tumours associated with E-cadherin inactivation. ..
  69. Ciechomska I, Goemans G, Skepper J, Tolkovsky A. Bcl-2 complexed with Beclin-1 maintains full anti-apoptotic function. Oncogene. 2009;28:2128-41 pubmed publisher
    ..Hence, although Beclin-1 contains a BH3-only motif typical of pro-apoptotic proteins, it is a negligible modulator of Bcl-2's anti-apoptotic function. ..
  70. Tagami S, Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y. A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity. Oncogene. 2000;19:5736-46 pubmed
    ..These results suggest that RTN family proteins can modulate the anti-apoptotic activity of Bcl-XL and Bcl-2 by binding with them and can change their localization to the ER. ..
  71. Muthumani K, Choo A, PremKumar A, Hwang D, Thieu K, Desai B, et al. Human immunodeficiency virus type 1 (HIV-1) Vpr-regulated cell death: insights into mechanism. Cell Death Differ. 2005;12 Suppl 1:962-70 pubmed
    ..Further, we also discuss caveats and future directions for investigation of the interesting biology of this HIV accessory gene. ..
  72. Bigelow R, Chari N, Unden A, Spurgers K, Lee S, Roop D, et al. Transcriptional regulation of bcl-2 mediated by the sonic hedgehog signaling pathway through gli-1. J Biol Chem. 2004;279:1197-205 pubmed
    ..These studies further suggest that one consequence of the deregulation of shh signaling in BCC is the up-regulation of bcl-2. ..
  73. Del Gaizo Moore V, Brown J, Certo M, Love T, Novina C, Letai A. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest. 2007;117:112-21 pubmed
    ..Indeed, activator BH3-only occupation of BCL2 may prime cancer cells for death, offering a potential explanation for the marked chemosensitivity of certain cancers that express abundant BCL2, such as CLL and follicular lymphoma. ..
  74. Liang X, Kleeman L, Jiang H, Gordon G, Goldman J, Berry G, et al. Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J Virol. 1998;72:8586-96 pubmed
    ..These findings demonstrate that Beclin is a novel Bcl-2-interacting cellular protein that may play a role in antiviral host defense. ..
  75. Hirata H, Hinoda Y, Kikuno N, Suehiro Y, Shahryari V, Ahmad A, et al. Bcl2 -938C/A polymorphism carries increased risk of biochemical recurrence after radical prostatectomy. J Urol. 2009;181:1907-12 pubmed publisher
    ..To our knowledge this is the first report documenting that bcl2 promoter region -938 C/C genotype carriers more frequently show biochemical recurrence than -938C/A+A/A carriers. ..
  76. Zenz T, Benner A, Duhrsen U, Dürig J, Dohner H, Siffert W, et al. BCL2-938C>A polymorphism and disease progression in chronic lymphocytic leukemia. Leuk Lymphoma. 2009;50:1837-42 pubmed publisher
    ..The study re-emphasizes the need for large cohorts and validation in independent data sets before firm conclusions can be made about genotype-phenotype associations. ..
  77. Azad N, Iyer A, Vallyathan V, Wang L, Castranova V, Stehlik C, et al. Role of oxidative/nitrosative stress-mediated Bcl-2 regulation in apoptosis and malignant transformation. Ann N Y Acad Sci. 2010;1203:1-6 pubmed publisher
    ..We describe a novel mechanism of Bcl-2 regulation by *O(2)(-) and NO, providing a new dimension to reactive species-mediated Bcl-2 stability, apoptotic cell death, and cancer development. ..
  78. Ku B, Liang C, Jung J, Oh B. Evidence that inhibition of BAX activation by BCL-2 involves its tight and preferential interaction with the BH3 domain of BAX. Cell Res. 2011;21:627-41 pubmed publisher
  79. Huang F, Yang Z, Yu D, Wang J, Li R, Ding G. Sepia ink oligopeptide induces apoptosis in prostate cancer cell lines via caspase-3 activation and elevation of Bax/Bcl-2 ratio. Mar Drugs. 2012;10:2153-65 pubmed publisher
    ..Moreover, the Bax/Bcl-2expression ratio was increased. Concurrently, the expression of caspase-3 was upregulated. These data support our hypothesis that SIO has anticarcinogenic properties. ..
  80. McGill G, Horstmann M, Widlund H, Du J, Motyckova G, Nishimura E, et al. Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. Cell. 2002;109:707-18 pubmed
    ..This linkage helps explain the vital roles of both Mitf and Bcl2 in the melanocyte lineage and the well-known treatment resistance of melanoma. ..
  81. Zalckvar E, Berissi H, Mizrachy L, Idelchuk Y, Koren I, Eisenstein M, et al. DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy. EMBO Rep. 2009;10:285-92 pubmed publisher
  82. Lam M, Dubyak G, Chen L, Nunez G, Miesfeld R, Distelhorst C. Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes. Proc Natl Acad Sci U S A. 1994;91:6569-73 pubmed
    ..These findings suggest that BCL-2 either directly or indirectly regulates the flux of Ca2+ across the ER membrane, thereby abrogating Ca2+ signaling of apoptosis. ..
  83. Sastry K, Marin M, Nehete P, McConnell K, El Naggar A, McDonnell T. Expression of human immunodeficiency virus type I tat results in down-regulation of bcl-2 and induction of apoptosis in hematopoietic cells. Oncogene. 1996;13:487-93 pubmed
    ..While these results support reports in the literature of an active role for tat in inducing cell death in HIV-infected individuals, they point to a new mechanism involving Tat-mediated modulation of bcl-2 and bax. ..
  84. Lehnerdt G, Franz P, Bankfalvi A, Grehl S, Kelava A, Nuckel H, et al. The regulatory BCL2 promoter polymorphism (-938C>A) is associated with relapse and survival of patients with oropharyngeal squamous cell carcinoma. Ann Oncol. 2009;20:1094-9 pubmed publisher
    ..897, P = 0.013). The (-938C>A) SNP represents a potential novel prognostic marker in patients with OSCC that could help to identify a group of patients at high risk for relapse and death. ..
  85. Porichi O, Nikolaidou M, Apostolaki A, Tserkezoglou A, Arnogiannaki N, Kassanos D, et al. BCL-2, BAX and P53 expression profiles in endometrial carcinoma as studied by real-time PCR and immunohistochemistry. Anticancer Res. 2009;29:3977-82 pubmed
    ..7). The Bcl-2/bax ratio is increased in grade 3 tumors. Bax protein shows a strong tendency for expression in the third group of clinical staging (stage IIb, III and IV). Poorly differentiated tumors highly expressed mutated p53. ..
  86. Yang J, Liu X, Bhalla K, Kim C, Ibrado A, Cai J, et al. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 1997;275:1129-32 pubmed
    ..Overexpression of Bcl-2 prevented the efflux of cytochrome c from the mitochondria and the initiation of apoptosis. Thus, one possible role of Bcl-2 in prevention of apoptosis is to block cytochrome c release from mitochondria. ..
  87. Cheng E, Wei M, Weiler S, Flavell R, Mak T, Lindsten T, et al. BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell. 2001;8:705-11 pubmed
    ..Thus, in mammals, BH3 domain-only molecules activate multidomain proapoptotic members to trigger a mitochondrial pathway, which both releases cytochrome c to activate caspases and initiates caspase-independent mitochondrial dysfunction. ..
  88. Cartron P, Gallenne T, Bougras G, Gautier F, Manero F, Vusio P, et al. The first alpha helix of Bax plays a necessary role in its ligand-induced activation by the BH3-only proteins Bid and PUMA. Mol Cell. 2004;16:807-18 pubmed
    ..Thus, a specific interaction between Bax Halpha1 and their BH3 domains allows Bid and PUMA to function as "death agonists" of Bax, whereas Bad recruits Bax activity through a distinct pathway. ..
  89. Noble C, Dong J, Manser E, Song H. Bcl-xL and UVRAG cause a monomer-dimer switch in Beclin1. J Biol Chem. 2008;283:26274-82 pubmed publisher
    ..Furthermore, our data suggest that an alternative strategy for developing anti-cancer compounds would be to disrupt the Beclin1-dimer interface. ..
  90. Fletcher J, Meusburger S, Hawkins C, Riglar D, Lee E, Fairlie W, et al. Apoptosis is triggered when prosurvival Bcl-2 proteins cannot restrain Bax. Proc Natl Acad Sci U S A. 2008;105:18081-7 pubmed publisher
  91. Portier B, Taglialatela G. Bcl-2 localized at the nuclear compartment induces apoptosis after transient overexpression. J Biol Chem. 2006;281:40493-502 pubmed
    ..These results indicate that Bcl-2 has a dual role as both a protector and a killer and that the ability to switch roles depends on Bcl-2 subcellular localization. ..
  92. Azad N, Iyer A, Wang L, Lu Y, Medan D, Castranova V, et al. Nitric oxide-mediated bcl-2 stabilization potentiates malignant transformation of human lung epithelial cells. Am J Respir Cell Mol Biol. 2010;42:578-85 pubmed publisher