Genomes and Genes
Gene Symbol: Bcl2
Description: B cell leukemia/lymphoma 2
Alias: AW986256, Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik, apoptosis regulator Bcl-2
- He C, Bassik M, Moresi V, Sun K, Wei Y, Zou Z, et al. Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature. 2012;481:511-5 pubmed publisher..These mice (termed BCL2 AAA mice) contain knock-in mutations in BCL2 phosphorylation sites (Thr69Ala, Ser70Ala and Ser84Ala) that prevent ..
- Ziehr J, Sheibani N, Sorenson C. Alterations in cell-adhesive and migratory properties of proximal tubule and collecting duct cells from bcl-2 -/- mice. Am J Physiol Renal Physiol. 2004;287:F1154-63 pubmed..Therefore, alterations in cell-adhesive and migratory characteristics may be an early indicator of aberrant renal epithelial cell differentiation. ..
- Rajpal A, Cho Y, Yelent B, Koza Taylor P, Li D, Chen E, et al. Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan steroid receptor. EMBO J. 2003;22:6526-36 pubmed..Thus Nur77-mediated apoptosis in T cells involves Bcl-2 independent transcriptional activation of several known and novel apoptotic pathways. ..
- Bouillet P, Cory S, Zhang L, Strasser A, Adams J. Degenerative disorders caused by Bcl-2 deficiency prevented by loss of its BH3-only antagonist Bim. Dev Cell. 2001;1:645-53 pubmed..These results demonstrate that Bim levels set the threshold for initiation of apoptosis in several tissues and suggest that degenerative diseases might be alleviated by blocking BH3-only proteins. ..
- Zhan Y, Zhang Y, Gray D, Carrington E, Bouillet P, Ko H, et al. Defects in the Bcl-2-regulated apoptotic pathway lead to preferential increase of CD25 low Foxp3+ anergic CD4+ T cells. J Immunol. 2011;187:1566-77 pubmed publisher..This clonal functional diversion may help to curtail autoaggressiveness of escaped self-reactive CD4(+) T cells and thereby safeguard immunological tolerance. ..
- 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. ..
- Chipuk J, Fisher J, Dillon C, Kriwacki R, Kuwana T, Green D. Mechanism of apoptosis induction by inhibition of the anti-apoptotic BCL-2 proteins. Proc Natl Acad Sci U S A. 2008;105:20327-32 pubmed publisher..Our data show that the induction of apoptosis by inhibition of the anti-apoptotic BCL-2 repertoire requires "covert" levels of direct activators of BAX and BAK at the OMM. ..
- Kolluri S, Zhu X, Zhou X, Lin B, Chen Y, Sun K, et al. A short Nur77-derived peptide converts Bcl-2 from a protector to a killer. Cancer Cell. 2008;14:285-98 pubmed publisher..NuBCP-9s act as molecular switches to dislodge the Bcl-2 BH4 domain, exposing its BH3 domain, which in turn blocks the activity of antiapoptotic Bcl-X(L). ..
- de La Coste A, Mignon A, Fabre M, Gilbert E, Porteu A, Van Dyke T, et al. Paradoxical inhibition of c-myc-induced carcinogenesis by Bcl-2 in transgenic mice. Cancer Res. 1999;59:5017-22 pubmed..Thus, we have shown that Bcl-2 can have a tumor suppressor effect in vivo on c-myc-induced hepatocarcinogenesis during the emergence of neoplastic foci. ..
- 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. ..
- Limana F, Urbanek K, Chimenti S, Quaini F, Leri A, Kajstura J, et al. bcl-2 overexpression promotes myocyte proliferation. Proc Natl Acad Sci U S A. 2002;99:6257-62 pubmed..Taken together, these observations reveal a previously uncharacterized replication-enhancing function of Bcl-2 in myocytes in vivo in the absence of stressful conditions. ..
- Letai A, Sorcinelli M, Beard C, Korsmeyer S. Antiapoptotic BCL-2 is required for maintenance of a model leukemia. Cancer Cell. 2004;6:241-9 pubmed..This suggests a generalizable model in which aberrations inherent to cancer generate tonic death signals that would otherwise kill the cell if not opposed by a requisite apoptotic defect(s). ..
- Ogilvy S, Metcalf D, Print C, Bath M, Harris A, Adams J. Constitutive Bcl-2 expression throughout the hematopoietic compartment affects multiple lineages and enhances progenitor cell survival. Proc Natl Acad Sci U S A. 1999;96:14943-8 pubmed..Thus, Bcl-2 has multiple effects on the hematopoietic system. These mice should help to further clarify the role of apoptosis in the development and homeostasis of this compartment. ..
- Yamashita J, Datta N, Chun Y, Yang D, Carey A, Kreider J, et al. Role of Bcl2 in osteoclastogenesis and PTH anabolic actions in bone. J Bone Miner Res. 2008;23:621-32 pubmedB-cell leukemia/lymphoma 2 (Bcl2) is a proto-oncogene best known for its ability to suppress cell death. However, the role of Bcl2 in the skeletal system is unknown...
- Cory S, Adams J. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2:647-56 pubmed..The Bcl2 family of intracellular proteins is the central regulator of caspase activation, and its opposing factions of anti- ..
- Nakajima H, Leonard W. Role of Bcl-2 in alpha beta T cell development in mice deficient in the common cytokine receptor gamma-chain: the requirement for Bcl-2 differs depending on the TCR/MHC affinity. J Immunol. 1999;162:782-90 pubmed
- Willis S, Fletcher J, Kaufmann T, van Delft M, Chen L, Czabotar P, et al. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science. 2007;315:856-9 pubmed..Our results indicate that BH3-only proteins induce apoptosis at least primarily by engaging the multiple pro-survival relatives guarding Bax and Bak. ..
- Fedorov L, Schmittwolf C, Amann K, Thomas W, Müller A, Schubert H, et al. Renal failure causes early death of bcl-2 deficient mice. Mech Ageing Dev. 2006;127:600-9 pubmed..Such models can be useful to study the influence of bcl-2 or other gene deficiency in individual organs (or tissues) on development and ageing of whole organism. ..
- Lei X, Chen Y, Du G, Yu W, Wang X, Qu H, et al. Gossypol induces Bax/Bak-independent activation of apoptosis and cytochrome c release via a conformational change in Bcl-2. FASEB J. 2006;20:2147-9 pubmed..We conclude that gossypol converts the antiapoptotic molecule Bcl-2 into a proapoptotic molecule that can mediate the release of cyto c and induce apoptosis. ..
- Danial N, Walensky L, Zhang C, Choi C, Fisher J, Molina A, et al. Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nat Med. 2008;14:144-53 pubmed publisher..Furthermore, we show that BAD regulates the physiologic adaptation of beta cell mass during high-fat feeding. Our findings provide genetic proof of the bifunctional activities of BAD in both beta cell survival and insulin secretion. ..
- Zhang N, He Y. The antiapoptotic protein Bcl-xL is dispensable for the development of effector and memory T lymphocytes. J Immunol. 2005;174:6967-73 pubmed..These results indicate that Bcl-x is dispensable for the generation of effector and memory T lymphocytes and suggest that costimulation of T lymphocytes promotes their survival through a Bcl-x(L) independent mechanism. ..
- Wu Z, Lu H, Sheng J, Li L. Inductive microRNA-21 impairs anti-mycobacterial responses by targeting IL-12 and Bcl-2. FEBS Lett. 2012;586:2459-67 pubmed publisher..Additionally, miR-21 also promoted dendritic cell (DC) apoptosis by targeting Bcl-2. Therefore, miR-21 may potentially be involved in fine-tuning of the anti-mycobacterial Th1 response and in regulating the efficacy of BCG vaccination. ..
- Tardivel A, Tinel A, Lens S, Steiner Q, Sauberli E, Wilson A, et al. The anti-apoptotic factor Bcl-2 can functionally substitute for the B cell survival but not for the marginal zone B cell differentiation activity of BAFF. Eur J Immunol. 2004;34:509-18 pubmed..These results suggest that BAFF is required not only to inhibit apoptosis of maturating B cells, but also to promote differentiation events, in particular those leading to the generation of marginal zone B cells. ..
- Thorp E, Li Y, Bao L, Yao P, Kuriakose G, Rong J, et al. Brief report: increased apoptosis in advanced atherosclerotic lesions of Apoe-/- mice lacking macrophage Bcl-2. Arterioscler Thromb Vasc Biol. 2009;29:169-72 pubmed publisher..b>Bcl2(flox)-LysMCre mice were created as a model of macrophage Bcl-2 deficiency...
- Coultas L, Bouillet P, Stanley E, Brodnicki T, Adams J, Strasser A. Proapoptotic BH3-only Bcl-2 family member Bik/Blk/Nbk is expressed in hemopoietic and endothelial cells but is redundant for their programmed death. Mol Cell Biol. 2004;24:1570-81 pubmed..These results indicate that any function of Bik in programmed cell death and stress-induced apoptosis must overlap that of other BH3-only proteins. ..
- Zhu Y, Swanson B, Wang M, Hildeman D, Schaefer B, Liu X, et al. Constitutive association of the proapoptotic protein Bim with Bcl-2-related proteins on mitochondria in T cells. Proc Natl Acad Sci U S A. 2004;101:7681-6 pubmed..Our results indicate that, in T cells, Bim function is regulated by interaction with Bcl-2 family members on mitochondria rather than by sequestration to the microtubules. ..
- Mogga S, Mustafa T, Sviland L, Nilsen R. Increased Bcl-2 and reduced Bax expression in infected macrophages in slowly progressive primary murine Mycobacterium tuberculosis infection. Scand J Immunol. 2002;56:383-91 pubmed..We conclude that overexpression of Bcl-2 in Mphis containing MTB may be associated with intracellular survival of the bacilli, thus demonstrating one way by which MTB can escape the host's cellular response and killing. ..
- Opferman J, Letai A, Beard C, Sorcinelli M, Ong C, Korsmeyer S. Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature. 2003;426:671-6 pubmed..Thus, MCL-1, which selectively inhibits the proapoptotic protein BIM, is essential both early in lymphoid development and later on in the maintenance of mature lymphocytes. ..
- Deckwerth T, Easton R, Knudson C, Korsmeyer S, Johnson E. Placement of the BCL2 family member BAX in the death pathway of sympathetic neurons activated by trophic factor deprivation. Exp Neurol. 1998;152:150-62 pubmedThe BCL2 family member BAX is required for the induction of apoptosis in neonatal sympathetic neurons after NGF withdrawal. Bax-deficient sympathetic neurons are NGF-independent for survival...
- Nakayama K, Negishi I, Kuida K, Sawa H, Loh D. Targeted disruption of Bcl-2 alpha beta in mice: occurrence of gray hair, polycystic kidney disease, and lymphocytopenia. Proc Natl Acad Sci U S A. 1994;91:3700-4 pubmed..Surprisingly, the nervous system, intestines, and skin appear normal despite the fact that these organs show high levels of endogenous Bcl-2 expression in normal mice. ..
- Michaelidis T, Sendtner M, Cooper J, Airaksinen M, Holtmann B, Meyer M, et al. Inactivation of bcl-2 results in progressive degeneration of motoneurons, sympathetic and sensory neurons during early postnatal development. Neuron. 1996;17:75-89 pubmed
- Sentman C, Shutter J, Hockenbery D, Kanagawa O, Korsmeyer S. bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell. 1991;67:879-88 pubmed..This transgenic model indicates that multiple death pathways operate within the thymus that can be distinguished by their dependence on bcl-2. ..
- Strasser A, Whittingham S, Vaux D, Bath M, Adams J, Cory S, et al. Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc Natl Acad Sci U S A. 1991;88:8661-5 pubmedThe biological functions of the BCL2 gene were investigated in transgenic mice harboring human BCL2 cDNA under the control of an immunoglobulin heavy chain enhancer (E mu)...
- Veis D, Sorenson C, Shutter J, Korsmeyer S. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell. 1993;75:229-40 pubmed..The abnormalities in these loss of function mice argue that Bcl-2 is a death repressor molecule functioning in an antioxidant pathway. ..
- Sorenson C, Rogers S, Korsmeyer S, Hammerman M. Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice. Am J Physiol. 1995;268:F73-81 pubmed..During 3 days in culture, growth and development of metanephroi from bcl-2 (-/-) embryos were visibly reduced compared with those from bcl-2 (+/-) embryos.(ABSTRACT TRUNCATED AT 250 WORDS)..
- Linette G, Li Y, Roth K, Korsmeyer S. Cross talk between cell death and cell cycle progression: BCL-2 regulates NFAT-mediated activation. Proc Natl Acad Sci U S A. 1996;93:9545-52 pubmed..Thus, select genetic aberrations in the apoptotic pathway reveal a cell autonomous coregulation of activation. ..
- McDonnell T, Deane N, Platt F, Nunez G, Jaeger U, McKearn J, et al. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell. 1989;57:79-88 pubmed..bcl-2-Ig transgenic mice document a prospective role for the t(14;18) in B cell growth and the pathogenesis of follicular lymphoma. ..
- Knudson C, Korsmeyer S. Bcl-2 and Bax function independently to regulate cell death. Nat Genet. 1997;16:358-63 pubmed..In contrast, overexpression of Bcl-2 still repressed apoptosis in the absence of Bax. While an in vivo competition exists between Bax and Bcl-2, each is able to regulate apoptosis independently. ..
- Akashi K, Kondo M, von Freeden Jeffry U, Murray R, Weissman I. Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice. Cell. 1997;89:1033-41 pubmed..We propose cell survival signals to be the principal function of IL-7R engagement in thymic and T cell development. ..
- Strasser A, Harris A, Bath M, Cory S. Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature. 1990;348:331-3 pubmed..Suprisingly, the tumours derive from a cell with the hallmarks of a primitive haemopoietic cell, perhaps a lymphoid-committed stem cell. ..
- Linette G, Hess J, Sentman C, Korsmeyer S. Peripheral T-cell lymphoma in lckpr-bcl-2 transgenic mice. Blood. 1995;86:1255-60 pubmed..These data provide support for the thesis that violation of homeostasis through the repression of cell death can be a primary mechanism of tumorigenesis in multiple lineages. ..
- Strasser A, Harris A, Cory S. bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell. 1991;67:889-99 pubmed..These observations, together with previous findings on B cells, suggest that modulated bcl-2 expression is a determinant of life and death in normal lymphocytes. ..
- Matsuzaki Y, Nakayama K, Tomita T, Isoda M, Loh D, Nakauchi H. Role of bcl-2 in the development of lymphoid cells from the hematopoietic stem cell. Blood. 1997;89:853-62 pubmed..In addition, lymphopoiesis from fetal liver HSC appears to be less dependent on bcl-2 than adult bone marrow HSC. ..
- Maraskovsky E, O Reilly L, Teepe M, Corcoran L, Peschon J, Strasser A. Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1-/- mice. Cell. 1997;89:1011-9 pubmed..These results provide evidence that blocking apoptosis is the essential function of IL-7R during differentiation and activation of T lymphocytes and that pre-TCR signaling blocks a pathway to apoptosis that is insensitive to Bcl-2. ..
- Nakayama K, Negishi I, Kuida K, Shinkai Y, Louie M, Fields L, et al. Disappearance of the lymphoid system in Bcl-2 homozygous mutant chimeric mice. Science. 1993;261:1584-8 pubmed..T and B cells with no Bcl-2 disappeared from the bone marrow, thymus, and periphery by 4 weeks of age. Thus, Bcl-2 was dispensable for lymphocyte maturation, but was required for a stable immune system after birth. ..
- Kamada S, Shimono A, Shinto Y, Tsujimura T, Takahashi T, Noda T, et al. bcl-2 deficiency in mice leads to pleiotropic abnormalities: accelerated lymphoid cell death in thymus and spleen, polycystic kidney, hair hypopigmentation, and distorted small intestine. Cancer Res. 1995;55:354-9 pubmed..Our bcl-2-/- mice also revealed novel defects in the small intestine, characterized by retarded development, accelerated exfoliation of epithelial cells, and very few mitotic progenitor cells. ..
- Zörnig M, Busch G, Beneke R, Gulbins E, Lang F, Ma A, et al. Survival and death of prelymphomatous B-cells from N-myc/bcl-2 double transgenic mice correlates with the regulation of intracellular Ca2+ fluxes. Oncogene. 1995;11:2165-74 pubmed..We hypothesize therefore that the regulation of intracellular Ca2+ concentrations represent one important parameter in the oncogenic cooperation between bcl-2 and N-myc. ..
- Moore N, Anderson G, Williams G, Owen J, Jenkinson E. Developmental regulation of bcl-2 expression in the thymus. Immunology. 1994;81:115-9 pubmed..The possible implications of these changes in bcl-2 expression regarding other facets of thymocyte development will be discussed. ..
- Novack D, Korsmeyer S. Bcl-2 protein expression during murine development. Am J Pathol. 1994;145:61-73 pubmed..The wide distribution of Bcl-2 in the developing mouse suggests that many immature cells require a death repressor molecule or that Bcl-2 may have roles beyond regulating developmental cell death. ..
- Kondo M, Akashi K, Domen J, Sugamura K, Weissman I. Bcl-2 rescues T lymphopoiesis, but not B or NK cell development, in common gamma chain-deficient mice. Immunity. 1997;7:155-62 pubmed..Therefore, the development of T, B, and NK cells may be influenced by distinct intracytoplasmic signaling cascades that are activated by coupling of gamma(c)-related receptors. ..
- Korsmeyer S. Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood. 1992;80:879-86 pubmed
- Miyashita T, Krajewski S, Krajewska M, Wang H, Lin H, Liebermann D, et al. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene. 1994;9:1799-805 pubmed..The findings suggest a potential mechanism by which p53 regulates apoptosis, as well as responses to radiation and chemotherapeutic drugs in cancer. ..
- Wang K, Yin X, Chao D, Milliman C, Korsmeyer S. BID: a novel BH3 domain-only death agonist. Genes Dev. 1996;10:2859-69 pubmed..This BH3-only molecule supports BH3 as a death domain and favors a model in which BID represents a death ligand for the membrane-bound receptor BAX. ..
- 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. ..
- 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. ..