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Gene Review

BCL2  -  B-cell CLL/lymphoma 2

Homo sapiens

Synonyms: Apoptosis regulator Bcl-2, Bcl-2, PPP1R50
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Disease relevance of BCL2


Psychiatry related information on BCL2


High impact information on BCL2

  • Moreover, BCL-XL, BCL-2, and BAX can form ion-conductive pores in artificial membranes [7].
  • An expanding family of BCL-2 related proteins share homology, clustered within four conserved regions, namely BCL-2 homology (BH1-4) domains, which control the ability of these proteins to dimerize and function as regulators of apoptosis [7].
  • BID and BAD possess the minimal death domain BH3, and the phosphorylation of BAD connects proximal survival signals to the BCL-2 family [7].
  • BCL-2 family: regulators of cell death [7].
  • BCL-2 can rescue maturation at several points of lymphocyte development [7].

Chemical compound and disease context of BCL2


Biological context of BCL2


Anatomical context of BCL2


Associations of BCL2 with chemical compounds

  • BAD antagonizes both the cell cycle and antiapoptotic functions of BCL2 and BCL-x(L) through BH3 binding [22].
  • DeltaMEK1:ER+BCL2 cells remained viable for at least 3 days after estradiol deprivation, whereas viability was readily lost upon withdrawal of beta-estradiol in the MEK1-responsive cells which lacked BCL2 overexpression [23].
  • However, beta-carotene-induced expression changes of BAX and other BCL2 pathway genes did not lead to the predicted induction of apoptosis in the A375 cells [24].
  • No change in BCL2 expression was found after exposure to IC(50) concentrations of flavopiridol [25].
  • Multidrug resistance can be caused by the membrane-bound multidrug-resistance-associated protein, the detoxifying glutathione metabolism, the antiapoptotic protein BCL2, and changes in levels or activity of the topoisomerase enzymes [26].
  • The induction of Bcl-2 inhibited apoptosis induced by serum starvation or etoposide, and PKCepsilon activation attenuated etoposide-induced caspase-3 cleavage [27].
  • A total of 19 patients with the lowest levels of BCL2 protein expression were biologically and clinically heterogeneous; 5 patients exhibited high-level BCL2 RNA expression and 4 were fludarabine resistant [28].

Physical interactions of BCL2

  • E1B-19K is a BCL2 homolog that binds and inactivates proapoptotic BAK and BAX [29].
  • Bcl2/adenovirus EIB 19kD-interacting protein 3 (BNIP3) is a cell death factor that is a member of the Bcl-2 proapoptotic family recently shown to induce necrosis rather than apoptosis [30].
  • Detailed promoter analysis and gel shift assays identified three GLI binding sites in the human BCL2 cis-regulatory region [31].
  • The proapoptotic effect of BAX is negatively regulated by its binding with BCL-2 [32].
  • OBJECTIVE: BAG-1 has anti-apoptotic actions and is known to bind BCL-2 and steroid receptors [33].

Enzymatic interactions of BCL2

  • Expression of a series of wild-type and dominant-negative kinases indicated an ASK1/Jun N-terminal protein kinase 1 (JNK1) pathway phosphorylated BCL-2 in vivo [34].
  • BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M [34].
  • Hybridization studies with various DNA probes from the IGH locus as well as the BCL2 gene demonstrated that the mu-constant gene was deleted on the functional IGH allele of FL-318G cells, and that the cells produced abundant productive gamma-chain messages [35].

Regulatory relationships of BCL2


Other interactions of BCL2

  • Survival probability depends on multiple biologic factors, including overexpression of Bcl2, p53, Bax, Bcl-X(L), MIB1, and apoptotic index [41].
  • Alterations in 2p, 3q, 13, and 18q were not associated with N-MYC, BCL6, RB, or BCL2 alterations, respectively, suggesting that other genes may be the targets of these genetic abnormalities in MCLs [42].
  • These and other data suggest that genes at 18q21.3, other than BCL2 and FVT1, may be targets for translocation in certain subgroups of B-NHL [4].
  • Northern blotting and immunoblotting analyses revealed that the expression level of MCL1, a member of the BCL2 family, was increased by VEGF [43].
  • The expression of BCL-2 was higher in M-Mphi, and M-CSF withdrawal down-regulated the expression [40].
  • Deletion of any of the BH domains from Bcl2 abrogates the ability of Bcl2 to interact with APE1 as well as the inhibitory effects of Bcl2 on APE1 activity and AP site repair [44].

Analytical, diagnostic and therapeutic context of BCL2

  • However, it is not known whether somatic mutations that alter BCL2 proteins occur in vivo or whether they result from chemotherapy or arise through other mechanisms [3].
  • The presence of BCL2 rearrangements did not significantly affect overall survival (OS) or disease-free survival (DFS) [45].
  • To elucidate the molecular mechanisms underlying this inhibitory effect of VEGF, we examined expression levels of BCL2 family proteins in CMK86, a human leukemia cell line, after treatment with VEGF [43].
  • Quantitative flow cytometry for BCL2 and MYC expression showed abundant expression of both proteins in all three lines [46].
  • As demonstrated by Southern blot analysis, BCL2 at 18q21, but not MLL/ALL1 at 11q23, was involved in these translocations [47].


  1. Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. McGill, G.G., Horstmann, M., Widlund, H.R., Du, J., Motyckova, G., Nishimura, E.K., Lin, Y.L., Ramaswamy, S., Avery, W., Ding, H.F., Jordan, S.A., Jackson, I.J., Korsmeyer, S.J., Golub, T.R., Fisher, D.E. Cell (2002) [Pubmed]
  2. Activation of MYC in a masked t(8;17) translocation results in an aggressive B-cell leukemia. Gauwerky, C.E., Huebner, K., Isobe, M., Nowell, P.C., Croce, C.M. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  3. Frequent incidence of somatic mutations in translocated BCL2 oncogenes of non-Hodgkin's lymphomas. Tanaka, S., Louie, D.C., Kant, J.A., Reed, J.C. Blood (1992) [Pubmed]
  4. B-cell non-Hodgkin's lymphoma cell line (Karpas 1106) with complex translocation involving 18q21.3 but lacking BCL2 rearrangement and expression. Nacheva, E., Dyer, M.J., Metivier, C., Jadayel, D., Stranks, G., Morilla, R., Heward, J.M., Holloway, T., O'Connor, S., Bevan, P.C. Blood (1994) [Pubmed]
  5. Bcl2 and human papilloma virus 16 as predictors of outcome following concurrent chemoradiation for advanced oropharyngeal cancer. Nichols, A.C., Finkelstein, D.M., Faquin, W.C., Westra, W.H., Mroz, E.A., Kneuertz, P., Begum, S., Michaud, W.A., Busse, P.M., Clark, J.R., Rocco, J.W. Clin. Cancer Res. (2010) [Pubmed]
  6. Apoptosis of CD4+ T and Natural Killer Cells in Alzheimer's Disease. Schindowski, K., Peters, J., Gorriz, C., Schramm, U., Weinandi, T., Leutner, S., Maurer, K., Fr??lich, L., M??ller, W.E., Eckert, A. Pharmacopsychiatry (2006) [Pubmed]
  7. BCL-2 family: regulators of cell death. Chao, D.T., Korsmeyer, S.J. Annu. Rev. Immunol. (1998) [Pubmed]
  8. Decreased C-MYC and BCL2 expression correlates with methylprednisolone-mediated inhibition of Raji lymphoma growth. Morris, G., DeNardo, S.J., DeNardo, G.L., Leshchinsky, T., Wu, B., Mack, P.C., Winthrop, M.D., Gumerlock, P.H. Biochem. Mol. Med. (1997) [Pubmed]
  9. Predicting chemoresistance in human malignant glioma cells: the role of molecular genetic analyses. Weller, M., Rieger, J., Grimmel, C., Van Meir, E.G., De Tribolet, N., Krajewski, S., Reed, J.C., von Deimling, A., Dichgans, J. Int. J. Cancer (1998) [Pubmed]
  10. Gemcitabine cytotoxicity of human malignant glioma cells: modulation by antioxidants, BCL-2 and dexamethasone. Rieger, J., Durka, S., Streffer, J., Dichgans, J., Weller, M. Eur. J. Pharmacol. (1999) [Pubmed]
  11. Down regulation of bcl2 expression in invasive ductal carcinomas is both estrogen- and progesterone-receptor dependent and associated with poor prognostic factors. Park, S.H., Kim, H., Song, B.J. Pathol. Oncol. Res. (2002) [Pubmed]
  12. Enhancement of the efficacy of chemotherapy for lung cancer by simultaneous suppression of multidrug resistance and antiapoptotic cellular defense: novel multicomponent delivery system. Pakunlu, R.I., Wang, Y., Tsao, W., Pozharov, V., Cook, T.J., Minko, T. Cancer Res. (2004) [Pubmed]
  13. mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Majumder, P.K., Febbo, P.G., Bikoff, R., Berger, R., Xue, Q., McMahon, L.M., Manola, J., Brugarolas, J., McDonnell, T.J., Golub, T.R., Loda, M., Lane, H.A., Sellers, W.R. Nat. Med. (2004) [Pubmed]
  14. B-cell non-Hodgkin's lymphoma: evidence for the t (14;18) translocation in all hematopoietic cell lineages. Yarkoni, S., Lishner, M., Tangi, I., Nagler, A., Lorberboum-Galski, H. J. Natl. Cancer Inst. (1996) [Pubmed]
  15. The Bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients. Silvestrini, R., Veneroni, S., Daidone, M.G., Benini, E., Boracchi, P., Mezzetti, M., Di Fronzo, G., Rilke, F., Veronesi, U. J. Natl. Cancer Inst. (1994) [Pubmed]
  16. Traps to catch unwary oncogenes. Hueber, A.O., Evan, G.I. Trends Genet. (1998) [Pubmed]
  17. BCL2 translocation frequency rises with age in humans. Liu, Y., Hernandez, A.M., Shibata, D., Cortopassi, G.A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  18. miR-15 and miR-16 induce apoptosis by targeting BCL2. Cimmino, A., Calin, G.A., Fabbri, M., Iorio, M.V., Ferracin, M., Shimizu, M., Wojcik, S.E., Aqeilan, R.I., Zupo, S., Dono, M., Rassenti, L., Alder, H., Volinia, S., Liu, C.G., Kipps, T.J., Negrini, M., Croce, C.M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  19. Myeloid cell leukemia 1 is phosphorylated through two distinct pathways, one associated with extracellular signal-regulated kinase activation and the other with G2/M accumulation or protein phosphatase 1/2A inhibition. Domina, A.M., Smith, J.H., Craig, R.W. J. Biol. Chem. (2000) [Pubmed]
  20. BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma. Iqbal, J., Sanger, W.G., Horsman, D.E., Rosenwald, A., Pickering, D.L., Dave, B., Dave, S., Xiao, L., Cao, K., Zhu, Q., Sherman, S., Hans, C.P., Weisenburger, D.D., Greiner, T.C., Gascoyne, R.D., Ott, G., Müller-Hermelink, H.K., Delabie, J., Braziel, R.M., Jaffe, E.S., Campo, E., Lynch, J.C., Connors, J.M., Vose, J.M., Armitage, J.O., Grogan, T.M., Staudt, L.M., Chan, W.C. Am. J. Pathol. (2004) [Pubmed]
  21. Expression of genes encoding innate host defense molecules in normal human monocytes in response to Candida albicans. Kim, H.S., Choi, E.H., Khan, J., Roilides, E., Francesconi, A., Kasai, M., Sein, T., Schaufele, R.L., Sakurai, K., Son, C.G., Greer, B.T., Chanock, S., Lyman, C.A., Walsh, T.J. Infect. Immun. (2005) [Pubmed]
  22. BCL2 family in DNA damage and cell cycle control. Zinkel, S., Gross, A., Yang, E. Cell Death Differ. (2006) [Pubmed]
  23. Combined effects of aberrant MEK1 activity and BCL2 overexpression on relieving the cytokine dependency of human and murine hematopoietic cells. Blalock, W.L., Moye, P.W., Chang, F., Pearce, M., Steelman, L.S., McMahon, M., McCubrey, J.A. Leukemia (2000) [Pubmed]
  24. The microarray expression analysis identifies BAX as a mediator of beta-carotene effects on apoptosis. Bodzioch, M., Dembinska-Kiec, A., Hartwich, J., Lapicka-Bodzioch, K., Banas, A., Polus, A., Grzybowska, J., Wybranska, I., Dulinska, J., Gil, D., Laidler, P., Placha, W., Zawada, M., Balana-Nowak, A., Sacha, T., Kiec-Wilk, B., Skotnicki, A., Moehle, C., Langmann, T., Schmitz, G. Nutrition and cancer. (2005) [Pubmed]
  25. The effect of flavopiridol on the growth of p16+ and p16- melanoma cell lines. Robinson, W.A., Miller, T.L., Harrold, E.A., Bemis, L.T., Brady, B.M., Nelson, R.P. Melanoma Res. (2003) [Pubmed]
  26. Circumvention of multidrug resistance in genitourinary tumors. van Brussel, J.P., Mickisch, G.H. International journal of urology : official journal of the Japanese Urological Association. (1998) [Pubmed]
  27. A protein kinase Cepsilon-anti-apoptotic kinase signaling complex protects human vascular endothelial cells against apoptosis through induction of Bcl-2. Steinberg, R., Harari, O.A., Lidington, E.A., Boyle, J.J., Nohadani, M., Samarel, A.M., Ohba, M., Haskard, D.O., Mason, J.C. J. Biol. Chem. (2007) [Pubmed]
  28. BCL2 expression in chronic lymphocytic leukemia: lack of association with the BCL2 938A>C promoter single nucleotide polymorphism. Majid, A., Tsoulakis, O., Walewska, R., Gesk, S., Siebert, R., Kennedy, D.B., Dyer, M.J. Blood (2008) [Pubmed]
  29. Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus. Berk, A.J. Oncogene (2005) [Pubmed]
  30. HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Sowter, H.M., Ratcliffe, P.J., Watson, P., Greenberg, A.H., Harris, A.L. Cancer Res. (2001) [Pubmed]
  31. Activation of the BCL2 promoter in response to Hedgehog/GLI signal transduction is predominantly mediated by GLI2. Regl, G., Kasper, M., Schnidar, H., Eichberger, T., Neill, G.W., Philpott, M.P., Esterbauer, H., Hauser-Kronberger, C., Frischauf, A.M., Aberger, F. Cancer Res. (2004) [Pubmed]
  32. The potential role of BAX and BCL-2 expression in diffuse alveolar damage. Guinee, D., Brambilla, E., Fleming, M., Hayashi, T., Rahn, M., Koss, M., Ferrans, V., Travis, W. Am. J. Pathol. (1997) [Pubmed]
  33. BAG-1 expression in normal and neoplastic endometrium. Moriyama, T., Littell, R.D., Debernardo, R., Oliva, E., Lynch, M.P., Rueda, B.R., Duska, L.R. Gynecol. Oncol. (2004) [Pubmed]
  34. BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Yamamoto, K., Ichijo, H., Korsmeyer, S.J. Mol. Cell. Biol. (1999) [Pubmed]
  35. Immunoglobulin heavy chain class switching, mu to gamma, in a human lymphoma cell line FL-318 carrying a t(14;18)(q32;q21) chromosomal translocation. Kadowaki, N., Amakawa, R., Hayashi, T., Akasaka, T., Yabumoto, K., Ohno, H., Fukuhara, S., Okuma, M. Leukemia (1995) [Pubmed]
  36. Inhibitory effect of Bcl-2 on p53-mediated transactivation following genotoxic stress. Zhan, Q., Kontny, U., Iglesias, M., Alamo, I., Yu, K., Hollander, M.C., Woodworth, C.D., Fornace, A.J. Oncogene (1999) [Pubmed]
  37. Overexpression of BCL2 blocks TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human lung cancer cells. Sun, S.Y., Yue, P., Zhou, J.Y., Wang, Y., Choi Kim, H.R., Lotan, R., Wu, G.S. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  38. Both Stat3-activation and Stat3-independent BCL2 downregulation are important for interleukin-6-induced apoptosis of 1A9-M cells. Oritani, K., Tomiyama, Y., Kincade, P.W., Aoyama, K., Yokota, T., Matsumura, I., Kanakura, Y., Nakajima, K., Hirano, T., Matsuzawa, Y. Blood (1999) [Pubmed]
  39. Regulation of MCL1 through a serum response factor/Elk-1-mediated mechanism links expression of a viability-promoting member of the BCL2 family to the induction of hematopoietic cell differentiation. Townsend, K.J., Zhou, P., Qian, L., Bieszczad, C.K., Lowrey, C.H., Yen, A., Craig, R.W. J. Biol. Chem. (1999) [Pubmed]
  40. Catalase plays a critical role in the CSF-independent survival of human macrophages via regulation of the expression of BCL-2 family. Komuro, I., Yasuda, T., Iwamoto, A., Akagawa, K.S. J. Biol. Chem. (2005) [Pubmed]
  41. Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays. García, J.F., Camacho, F.I., Morente, M., Fraga, M., Montalbán, C., Alvaro, T., Bellas, C., Castaño, A., Díez, A., Flores, T., Martin, C., Martinez, M.A., Mazorra, F., Menárguez, J., Mestre, M.J., Mollejo, M., Sáez, A.I., Sánchez, L., Piris, M.A. Blood (2003) [Pubmed]
  42. Increased number of chromosomal imbalances and high-level DNA amplifications in mantle cell lymphoma are associated with blastoid variants. Beà, S., Ribas, M., Hernández, J.M., Bosch, F., Pinyol, M., Hernández, L., García, J.L., Flores, T., González, M., López-Guillermo, A., Piris, M.A., Cardesa, A., Montserrat, E., Miró, R., Campo, E. Blood (1999) [Pubmed]
  43. Vascular endothelial growth factor inhibits apoptotic death in hematopoietic cells after exposure to chemotherapeutic drugs by inducing MCL1 acting as an antiapoptotic factor. Katoh, O., Takahashi, T., Oguri, T., Kuramoto, K., Mihara, K., Kobayashi, M., Hirata, S., Watanabe, H. Cancer Res. (1998) [Pubmed]
  44. Bcl2 inhibits abasic site repair by down-regulating APE1 endonuclease activity. Zhao, J., Gao, F., Zhang, Y., Wei, K., Liu, Y., Deng, X. J. Biol. Chem. (2008) [Pubmed]
  45. Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma. Kramer, M.H., Hermans, J., Wijburg, E., Philippo, K., Geelen, E., van Krieken, J.H., de Jong, D., Maartense, E., Schuuring, E., Kluin, P.M. Blood (1998) [Pubmed]
  46. Concurrent activation of MYC and BCL2 in B cell non-Hodgkin lymphoma cell lines by translocation of both oncogenes to the same immunoglobulin heavy chain locus. Dyer, M.J., Lillington, D.M., Bastard, C., Tilly, H., Lens, D., Heward, J.M., Stranks, G., Morilla, R., Monrad, S., Guglielmi, P., Kluin-Nelemans, J.C., Hagemeijer, A., Young, B.D., Catovsky, D. Leukemia (1996) [Pubmed]
  47. Characterization of a novel malignant B cell line with t(14;18) and t(4;11) established from a patient with acute monoblastic leukemia. de Kroon, J.F., Kluin-Nelemans, H.C., Kluin, P.M., Schuuring, E., van Bergen, C.A., Oving, I., Wessels, H., Willemze, R., Falkenburg, J.H. Exp. Hematol. (1997) [Pubmed]
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