Gene Symbol: Bcl2l11
Description: BCL2-like 11 (apoptosis facilitator)
Alias: 1500006F24Rik, Bim, Bod, bcl2-L-11, bcl-2-like protein 11, Bcl2 interacting mediator of cell death, bcl2-interacting mediator of cell death
Species: mouse
Products:     Bcl2l11

Top Publications

  1. Chen S, Dai Y, Pei X, Grant S. Bim upregulation by histone deacetylase inhibitors mediates interactions with the Bcl-2 antagonist ABT-737: evidence for distinct roles for Bcl-2, Bcl-xL, and Mcl-1. Mol Cell Biol. 2009;29:6149-69 pubmed publisher
    The Bcl-2 antagonist ABT-737 kills transformed cells in association with displacement of Bim from Bcl-2...
  2. Staton T, Lazarevic V, Jones D, Lanser A, Takagi T, Ishii S, et al. Dampening of death pathways by schnurri-2 is essential for T-cell development. Nature. 2011;472:105-9 pubmed publisher
    ..Our findings uncover a critical regulator of T-cell development that controls the balance between death and differentiation. ..
  3. Reckling S, Divanovic S, Karp C, Wojciechowski S, Belkaid Y, Hildeman D. Proapoptotic Bcl-2 family member Bim promotes persistent infection and limits protective immunity. Infect Immun. 2008;76:1179-85 pubmed
    ..response, most of the activated effector T cells die by apoptosis driven by the proapoptotic Bcl-2 family member Bim (Bcl-2-interacting mediator of death)...
  4. Wojciechowski S, Jordan M, Zhu Y, White J, Zajac A, Hildeman D. Bim mediates apoptosis of CD127(lo) effector T cells and limits T cell memory. Eur J Immunol. 2006;36:1694-706 pubmed
    ..The pro-apoptotic Bcl-2 family member, Bcl-2 interacting mediator of death (Bim) is critical for eliminating most effector T cells, while expression of CD127 (IL-7Ralpha) has been proposed to ..
  5. Hübner A, Cavanagh Kyros J, Rincon M, Flavell R, Davis R. Functional cooperation of the proapoptotic Bcl2 family proteins Bmf and Bim in vivo. Mol Cell Biol. 2010;30:98-105 pubmed publisher
    ..Studies of compound mutants with the related gene Bim demonstrated that Bim and Bmf exhibit partially redundant functions in vivo...
  6. Kim H, Tu H, Ren D, Takeuchi O, Jeffers J, Zambetti G, et al. Stepwise activation of BAX and BAK by tBID, BIM, and PUMA initiates mitochondrial apoptosis. Mol Cell. 2009;36:487-99 pubmed publisher
    ..The activator BH3s, tBID/BIM/PUMA, attack and expose the alpha1 helix of BAX, resulting in secondary disengagement of the alpha9 helix and ..
  7. Concannon C, Tuffy L, Weisová P, Bonner H, Davila D, Bonner C, et al. AMP kinase-mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis. J Cell Biol. 2010;189:83-94 pubmed publisher
    ..We show that the Bcl-2 homology domain 3 (BH3)-only protein Bim, a proapoptotic Bcl-2 family member, is activated in multiple excitotoxicity paradigms, mediates excitotoxic ..
  8. 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
    Apoptosis in activated T cells in vivo requires the proapoptotic Bcl-2 family member Bim. We show here that, despite its ability to bind LC8, a component of the microtubule dynein motor complex, most of the Bim in both healthy and ..
  9. Szymczak Workman A, Delgoffe G, Green D, Vignali D. Cutting edge: regulatory T cells do not mediate suppression via programmed cell death pathways. J Immunol. 2011;187:4416-20 pubmed publisher
    ..We show that Tregs are able to suppress the proliferation of conventional T cells that are resistant to apoptosis (Bim(-/-), Bim(-/-)Puma(-/-), Bcl-2 transgenic) or receptor-interacting serine-threonine kinase-dependent necrosis (also ..

More Information


  1. Fortner K, Bouillet P, Strasser A, Budd R. Apoptosis regulators Fas and Bim synergistically control T-lymphocyte homeostatic proliferation. Eur J Immunol. 2010;40:3043-53 pubmed publisher
    ..regulates apoptosis in response to repeated TCR stimulation, whereas the Bcl-2 homology domain 3-only protein Bim mediates cytokine withdrawal-induced apoptosis...
  2. Chen M, Huang L, Wang J. Deficiency of Bim in dendritic cells contributes to overactivation of lymphocytes and autoimmunity. Blood. 2007;109:4360-7 pubmed
    ..b>Bim, a BH3-only protein of the Bcl-2 family, was expressed at low levels in DCs and was significantly up-regulated by ..
  3. Hughes P, Belz G, Fortner K, Budd R, Strasser A, Bouillet P. Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity. Immunity. 2008;28:197-205 pubmed publisher
    ..We examined mice lacking the gene encoding Bim (Bcl2l11) and with the inactivating lpr mutation in the gene encoding Fas (Fas), designated Bcl2l11(-/-)Fas(lpr/lpr) mice...
  4. Siggs O, Arnold C, Huber C, Pirie E, Xia Y, Lin P, et al. The P4-type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrow. Nat Immunol. 2011;12:434-40 pubmed publisher
    ..Our data establish an essential, cell-autonomous and context-sensitive function for ATP11C, a putative aminophospholipid flippase, in B cell development. ..
  5. Hildeman D, Zhu Y, Mitchell T, Bouillet P, Strasser A, Kappler J, et al. Activated T cell death in vivo mediated by proapoptotic bcl-2 family member bim. Immunity. 2002;16:759-67 pubmed
    ..We also found that Vbeta8(+) T cells from Bim-deficient mice are resistant to SEB-induced deletion...
  6. McKenzie M, Jamieson E, Jansen E, Scott C, Huang D, Bouillet P, et al. Glucose induces pancreatic islet cell apoptosis that requires the BH3-only proteins Bim and Puma and multi-BH domain protein Bax. Diabetes. 2010;59:644-52 pubmed publisher
    ..overexpression of the prosurvival protein Bcl-2 or deficiency of the apoptosis initiating BH3-only proteins Bim or Puma, or the downstream apoptosis effector Bax, markedly reduced glucose- or ribose-induced killing of islets...
  7. Gavalda N, Perez Navarro E, García Martínez J, Marco S, Benito A, Alberch J. Bax deficiency promotes an up-regulation of Bim(EL) and Bak during striatal and cortical postnatal development, and after excitotoxic injury. Mol Cell Neurosci. 2008;37:663-72 pubmed publisher
    ..wild-type animals, Bax knockout mice showed region- and time-dependent increases in pro-apoptotic proteins Bak and Bim(EL)...
  8. Hinds M, Smits C, Fredericks Short R, Risk J, Bailey M, Huang D, et al. Bim, Bad and Bmf: intrinsically unstructured BH3-only proteins that undergo a localized conformational change upon binding to prosurvival Bcl-2 targets. Cell Death Differ. 2007;14:128-36 pubmed
    ..We show, using spectroscopic methods, that the BH3-only proteins Bim, Bad and Bmf are unstructured in the absence of binding partners...
  9. Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo M. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol. 2007;8:1353-62 pubmed
    ..T(reg) cell-induced effector CD4+ T cell death required the proapoptotic protein Bim, and effector CD4+ T cells incubated with T(reg) cells showed less activation of the prosurvival kinase Akt and ..
  10. Seo S, Chen Y, Ivanovska I, Ranger A, Hong S, Dawson V, et al. BAD is a pro-survival factor prior to activation of its pro-apoptotic function. J Biol Chem. 2004;279:42240-9 pubmed
    ..These findings suggest that BAD is more than an inert death factor in healthy cells; it is also a pro-survival factor, prior to its role in promoting cell death. ..
  11. 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.
  12. Jabbour A, Heraud J, Daunt C, Kaufmann T, Sandow J, O Reilly L, et al. Puma indirectly activates Bax to cause apoptosis in the absence of Bid or Bim. Cell Death Differ. 2009;16:555-63 pubmed publisher
    ..Puma rapidly induced apoptosis in cells lacking the BH3-only proteins, Bid and Bim. Puma expression resulted in activation of Bax, but Puma killing was not dependent on Bax or Bak alone as Puma ..
  13. Naik E, Michalak E, Villunger A, Adams J, Strasser A. Ultraviolet radiation triggers apoptosis of fibroblasts and skin keratinocytes mainly via the BH3-only protein Noxa. J Cell Biol. 2007;176:415-24 pubmed
    ..In the transformed derivatives, where Puma, unexpectedly, was not induced by UVR, Noxa had the dominant role and Bim a minor role...
  14. Huntington N, Puthalakath H, Gunn P, Naik E, Michalak E, Smyth M, et al. Interleukin 15-mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1. Nat Immunol. 2007;8:856-63 pubmed
    ..Here we identify Bim, Noxa and Mcl-1 as key regulators of IL-15-dependent survival of NK cells...
  15. Steimer D, Boyd K, Takeuchi O, Fisher J, Zambetti G, Opferman J. Selective roles for antiapoptotic MCL-1 during granulocyte development and macrophage effector function. Blood. 2009;113:2805-15 pubmed publisher
    ..The loss of mature neutrophils induced by Mcl-1 deletion was not rescued by genetic deletion of proapoptotic Bim and Puma or by exogenous cytokine treatment...
  16. Richter Larrea J, Robles E, Fresquet V, Beltran E, Rullan A, Agirre X, et al. Reversion of epigenetically mediated BIM silencing overcomes chemoresistance in Burkitt lymphoma. Blood. 2010;116:2531-42 pubmed publisher
    ..We previously reported the frequent inactivation of the proapoptotic BIM gene in B-cell lymphomas...
  17. Campbell K, Bath M, Turner M, Vandenberg C, Bouillet P, Metcalf D, et al. Elevated Mcl-1 perturbs lymphopoiesis, promotes transformation of hematopoietic stem/progenitor cells, and enhances drug resistance. Blood. 2010;116:3197-207 pubmed publisher
    ..Collectively, these results demonstrate that Mcl-1 overexpression renders hematopoietic cells refractory to many cytotoxic insults, perturbs lymphopoiesis and promotes malignant transformation of hematopoietic stem and progenitor cells. ..
  18. Akiyama T, Bouillet P, Miyazaki T, Kadono Y, Chikuda H, Chung U, et al. Regulation of osteoclast apoptosis by ubiquitylation of proapoptotic BH3-only Bcl-2 family member Bim. EMBO J. 2003;22:6653-64 pubmed
    ..apoptosis was associated with a rapid and sustained increase in the pro-apoptotic BH3-only Bcl-2 family member Bim. This was caused by the reduced ubiquitylation and proteasomal degradation of Bim that is mediated by c-Cbl...
  19. Day C, Puthalakath H, Skea G, Strasser A, Barsukov I, Lian L, et al. Localization of dynein light chains 1 and 2 and their pro-apoptotic ligands. Biochem J. 2004;377:597-605 pubmed
    ..of these motor complexes is to selectively sequester the pro-apoptotic 'BH3-only' (Bcl-2 homology 3-only) proteins, Bim (Bcl-2-interacting mediator of cell death) and Bmf (Bcl-2-modifying factor), and so regulate their cell death-..
  20. Suen A, Baldwin T. Proapoptotic protein Bim is differentially required during thymic clonal deletion to ubiquitous versus tissue-restricted antigens. Proc Natl Acad Sci U S A. 2012;109:893-8 pubmed publisher
    ..The proapoptotic Bcl-2 family member Bim is important for negative selection by inducing apoptosis in thymocytes receiving a strong signal through their ..
  21. Bouillet P, Metcalf D, Huang D, Tarlinton D, Kay T, Kontgen F, et al. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science. 1999;286:1735-8 pubmed
    Apoptosis can be triggered by members of the Bcl-2 protein family, such as Bim, that share only the BH3 domain with this family. Gene targeting in mice revealed important physiological roles for Bim...
  22. Ludwinski M, Sun J, Hilliard B, Gong S, Xue F, Carmody R, et al. Critical roles of Bim in T cell activation and T cell-mediated autoimmune inflammation in mice. J Clin Invest. 2009;119:1706-13 pubmed publisher
    b>Bim, the B cell lymphoma 2-interacting (Bcl2-interacting) mediator, maintains immunological tolerance by deleting autoreactive lymphocytes through apoptosis...
  23. Oliver P, Wang M, Zhu Y, White J, Kappler J, Marrack P. Loss of Bim allows precursor B cell survival but not precursor B cell differentiation in the absence of interleukin 7. J Exp Med. 2004;200:1179-87 pubmed
    ..versus B cell differentiation, the combined effects of lack of IL-7 and lack of the proapoptotic Bcl-2 relative, Bim, were studied. Bim is expressed to varying degrees in all B cell precursors and B cells...
  24. Koralov S, Muljo S, Galler G, Krek A, Chakraborty T, Kanellopoulou C, et al. Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell. 2008;132:860-74 pubmed publisher
    ..genes upregulated in Dicer-deficient pro-B cells; a top miR-17 approximately 92 target, the proapoptotic molecule Bim, was highly upregulated...
  25. O Reilly L, Kruse E, Puthalakath H, Kelly P, Kaufmann T, Huang D, et al. MEK/ERK-mediated phosphorylation of Bim is required to ensure survival of T and B lymphocytes during mitogenic stimulation. J Immunol. 2009;183:261-9 pubmed publisher
    ..b>Bim, a proapoptotic BH3-only member of the Bcl-2 family, can be regulated by MEK/ERK-mediated phosphorylation, which ..
  26. Steckley D, Karajgikar M, Dale L, Fuerth B, Swan P, Drummond Main C, et al. Puma is a dominant regulator of oxidative stress induced Bax activation and neuronal apoptosis. J Neurosci. 2007;27:12989-99 pubmed
    ..study, we demonstrate that, in cortical neurons, oxidative stress induces the expression of the BH3-only members Bim, Noxa, and Puma...
  27. Raynor J, Sholl A, Plas D, Bouillet P, Chougnet C, Hildeman D. IL-15 Fosters Age-Driven Regulatory T Cell Accrual in the Face of Declining IL-2 Levels. Front Immunol. 2013;4:161 pubmed publisher
    ..While we reported earlier that aged Treg have decreased expression of the pro-apoptotic molecule Bim and germline deletion of Bim promoted earlier accumulation of Treg, it remains unclear whether the effects of Bim ..
  28. Fischer S, Bouillet P, O Donnell K, Light A, Tarlinton D, Strasser A. Proapoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody-forming cells. Blood. 2007;110:3978-84 pubmed
    ..In this study, we examined the role of the BH3-only protein Bim, an initiator of apoptosis in the Bcl-2-regulated pathway, in the programmed cell death accompanying an immune ..
  29. Canté Barrett K, Gallo E, Winslow M, Crabtree G. Thymocyte negative selection is mediated by protein kinase C- and Ca2+-dependent transcriptional induction of bim [corrected]. J Immunol. 2006;176:2299-306 pubmed
    ..whereas negative selection requires the proapoptotic Bcl-2 family member Bcl-2-interacting mediator of cell death (Bim)...
  30. Enders A, Bouillet P, Puthalakath H, Xu Y, Tarlinton D, Strasser A. Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cells. J Exp Med. 2003;198:1119-26 pubmed
    ..Here we report that B lymphocytes lacking the pro-apoptotic Bcl-2 family member Bim are refractory to apoptosis induced by BCR ligation in vitro...
  31. Akhtar R, Klocke B, Strasser A, Roth K. Loss of BH3-only protein Bim inhibits apoptosis of hemopoietic cells in the fetal liver and male germ cells but not neuronal cells in bcl-x-deficient mice. J Histochem Cytochem. 2008;56:921-7 pubmed publisher
    ..In this study, we investigated the role for Bim, a BH3 domain only protein, in the embryonic lethality and increased developmental cell death in bcl-x-deficient ..
  32. Egle A, Harris A, Bouillet P, Cory S. Bim is a suppressor of Myc-induced mouse B cell leukemia. Proc Natl Acad Sci U S A. 2004;101:6164-9 pubmed
    ..b>Bim, a distant proapoptotic relative, is emerging as a major physiologic antagonist of Bcl2...
  33. Lindemann R, Newbold A, Whitecross K, Cluse L, Frew A, Ellis L, et al. Analysis of the apoptotic and therapeutic activities of histone deacetylase inhibitors by using a mouse model of B cell lymphoma. Proc Natl Acad Sci U S A. 2007;104:8071-6 pubmed
    ..but depended on activation of the intrinsic apoptotic pathway with the proapoptotic BH3-only proteins Bid and Bim playing an important role...
  34. Colli M, Nogueira T, Allagnat F, Cunha D, Gurzov E, Cardozo A, et al. Exposure to the viral by-product dsRNA or Coxsackievirus B5 triggers pancreatic beta cell apoptosis via a Bim / Mcl-1 imbalance. PLoS Pathog. 2011;7:e1002267 pubmed publisher
    ..Mcl-1 decrease results in the release of the BH3-only protein Bim, which activates the mitochondrial pathway of apoptosis...
  35. Tischner D, Gaggl I, Peschel I, Kaufmann M, Tuzlak S, Drach M, et al. Defective cell death signalling along the Bcl-2 regulated apoptosis pathway compromises Treg cell development and limits their functionality in mice. J Autoimmun. 2012;38:59-69 pubmed publisher
    ..We define a key role for the Bim/Bcl-2 axis in Treg cell development, homeostasis and function but exclude a role for apoptosis induction in ..
  36. Gray D, Kupresanin F, Berzins S, Herold M, O Reilly L, Bouillet P, et al. The BH3-only proteins Bim and Puma cooperate to impose deletional tolerance of organ-specific antigens. Immunity. 2012;37:451-62 pubmed publisher
    Although the proapoptotic BH3-only protein, Bim, is required for deletion of autoreactive thymocytes, Bim-deficient mice do not succumb to extensive organ-specific autoimmune disease...
  37. 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
    ..To test whether loss of the BH3-only protein Bim could prevent the cellular attrition caused by Bcl-2 deficiency, we generated mice lacking both genes...
  38. Weant A, Michalek R, Khan I, Holbrook B, Willingham M, Grayson J. Apoptosis regulators Bim and Fas function concurrently to control autoimmunity and CD8+ T cell contraction. Immunity. 2008;28:218-30 pubmed publisher
    ..Mutation of Bim, a proapoptotic protein in the intrinsic death pathway, or Fas, a tumor necrosis factor receptor (TNFR) superfamily ..
  39. Erlacher M, Labi V, Manzl C, Böck G, Tzankov A, Hacker G, et al. Puma cooperates with Bim, the rate-limiting BH3-only protein in cell death during lymphocyte development, in apoptosis induction. J Exp Med. 2006;203:2939-51 pubmed
    ..3-only proteins has been investigated in mice lacking the individual genes identifying rate-limiting roles for Bim (Bcl-2-interacting mediator of cell death) and Puma (p53-up-regulated modulator of apoptosis) in apoptosis ..
  40. Galehdar Z, Swan P, Fuerth B, Callaghan S, Park D, Cregan S. Neuronal apoptosis induced by endoplasmic reticulum stress is regulated by ATF4-CHOP-mediated induction of the Bcl-2 homology 3-only member PUMA. J Neurosci. 2010;30:16938-48 pubmed publisher
    ..We propose that this pathway may be an important therapeutic target relevant to a number of neurodegenerative conditions. ..
  41. Grayson J, Weant A, Holbrook B, Hildeman D. Role of Bim in regulating CD8+ T-cell responses during chronic viral infection. J Virol. 2006;80:8627-38 pubmed
    Apoptosis is critical for the development and maintenance of the immune system. The proapoptotic Bcl-2 family member Bim is important for normal immune system homeostasis...
  42. Harada H, Quearry B, Ruiz Vela A, Korsmeyer S. Survival factor-induced extracellular signal-regulated kinase phosphorylates BIM, inhibiting its association with BAX and proapoptotic activity. Proc Natl Acad Sci U S A. 2004;101:15313-7 pubmed
    ..A small interfering RNA knockdown of BIM confirms this BH3-only member is important for the cytokine-mediated homeostasis of hematopoietic cells...
  43. Puthalakath H, O Reilly L, Gunn P, Lee L, Kelly P, Huntington N, et al. ER stress triggers apoptosis by activating BH3-only protein Bim. Cell. 2007;129:1337-49 pubmed
    ..b>Bim, a proapoptotic BH3-only member of the Bcl-2 family is required for initiation of apoptosis induced by cytokine ..
  44. Bunk E, König H, Bernas T, Engel T, Henshall D, Kirby B, et al. BH3-only proteins BIM and PUMA in the regulation of survival and neuronal differentiation of newly generated cells in the adult mouse hippocampus. Cell Death Dis. 2010;1:e15 pubmed publisher
    ..The BH3-only proteins Bim and Puma have been shown to mediate trophic factor withdrawal- and anoikis-induced apoptosis in various systems...
  45. Marsden V, O Connor L, O Reilly L, Silke J, Metcalf D, Ekert P, et al. Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome. Nature. 2002;419:634-7 pubmed
    ..We conclude that Bcl-2 regulates a caspase activation programme independently of the cytochrome c/Apaf-1/caspase-9 'apoptosome', which seems to amplify rather than initiate the caspase cascade. ..
  46. 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
    ..TCRs, evident from a prominent increase in self-superantigen-specific Foxp3(+)V?5(+)CD4(+) T cells in BALB/c Bim(-/-) mice compared with control animals...
  47. Harder J, Libby R. BBC3 (PUMA) regulates developmental apoptosis but not axonal injury induced death in the retina. Mol Neurodegener. 2011;6:50 pubmed publisher
    ..Since the Bcl-2 family members BIM, BID, and BBC3 (PUMA) are powerful direct activators of BAX, we used mice deficient for each of these genes to ..
  48. Merino D, Giam M, Hughes P, Siggs O, Heger K, O Reilly L, et al. The role of BH3-only protein Bim extends beyond inhibiting Bcl-2-like prosurvival proteins. J Cell Biol. 2009;186:355-62 pubmed publisher
    ..must neutralize all of the prosurvival Bcl-2 family members, whereas the direct activation model proposes that Bim and Bid must activate Bax and Bak directly...
  49. Labi V, Erlacher M, Kiessling S, Manzl C, Frenzel A, O Reilly L, et al. Loss of the BH3-only protein Bmf impairs B cell homeostasis and accelerates gamma irradiation-induced thymic lymphoma development. J Exp Med. 2008;205:641-55 pubmed publisher
    ..Finally, Bmf-deficiency accelerated the development of gamma irradiation-induced thymic lymphomas. Our results demonstrate that Bmf plays a critical role in apoptosis signaling and can function as a tumor suppressor. ..
  50. Erlacher M, Michalak E, Kelly P, Labi V, Niederegger H, Coultas L, et al. BH3-only proteins Puma and Bim are rate-limiting for gamma-radiation- and glucocorticoid-induced apoptosis of lymphoid cells in vivo. Blood. 2005;106:4131-8 pubmed
    ..types of cultured cells, 3 BH3-only proteins, namely Puma (p53 up-regulated modulator of apoptosis), Noxa, and Bim (Bcl-2 interacting mediator of cell death), have been shown to initiate p53-dependent as well as p53-independent ..
  51. Wang P, Gilmore A, Streuli C. Bim is an apoptosis sensor that responds to loss of survival signals delivered by epidermal growth factor but not those provided by integrins. J Biol Chem. 2004;279:41280-5 pubmed
    ..The Bcl-2 homology 3 domain-only protein, Bim, has been proposed to have a key role in the apoptosis response of an epithelial cell line with reduced sensitivity ..
  52. Wali J, Rondas D, McKenzie M, Zhao Y, Elkerbout L, Fynch S, et al. The proapoptotic BH3-only proteins Bim and Puma are downstream of endoplasmic reticulum and mitochondrial oxidative stress in pancreatic islets in response to glucotoxicity. Cell Death Dis. 2014;5:e1124 pubmed publisher
    ..induce apoptosis of islet cells, and this requires the proapoptotic Bcl-2 homology domain 3 (BH3)-only proteins Bim and Puma. We studied the stress pathways induced by glucotoxicity in beta cells that result in apoptosis...
  53. Jorgensen T, McKee A, Wang M, Kushnir E, White J, Refaeli Y, et al. Bim and Bcl-2 mutually affect the expression of the other in T cells. J Immunol. 2007;179:3417-24 pubmed
    ..The antiapoptotic protein Bcl-2 and the proapoptotic protein Bim are particularly important in this process with the amount of Bcl-2 per cell dropping by about one-half when T ..
  54. Corazza N, Jakob S, Schaer C, Frese S, Keogh A, Stroka D, et al. TRAIL receptor-mediated JNK activation and Bim phosphorylation critically regulate Fas-mediated liver damage and lethality. J Clin Invest. 2006;116:2493-9 pubmed
    ..hepatocyte apoptosis through the activation of JNK and its downstream substrate, the proapoptotic Bcl-2 homolog Bim. Consistently, TRAIL- and Bim-deficient mice and wild-type mice treated with a JNK inhibitor were protected against ..
  55. 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
    ..show that Bax and Bak can mediate apoptosis without discernable association with the putative BH3-only activators (Bim, Bid, and Puma), even in cells with no Bim or Bid and reduced Puma...
  56. Pellegrini M, Bouillet P, Robati M, Belz G, Davey G, Strasser A. Loss of Bim increases T cell production and function in interleukin 7 receptor-deficient mice. J Exp Med. 2004;200:1189-95 pubmed
    ..BH3-only proteins such as Bim, which are distant proapoptotic members of the Bcl-2 family, are essential initiators of programmed cell death and ..
  57. Weber A, Paschen S, Heger K, Wilfling F, Frankenberg T, Bauerschmitt H, et al. BimS-induced apoptosis requires mitochondrial localization but not interaction with anti-apoptotic Bcl-2 proteins. J Cell Biol. 2007;177:625-36 pubmed
    ..Here, we analyze apoptosis induction by the BH3-only protein Bim(S)...
  58. Barthson J, Germano C, Moore F, Maida A, Drucker D, Marchetti P, et al. Cytokines tumor necrosis factor-? and interferon-? induce pancreatic ?-cell apoptosis through STAT1-mediated Bim protein activation. J Biol Chem. 2011;286:39632-43 pubmed publisher
    ..The combination of TNF-? + IFN-? induced DP5, p53 up-regulated modulator of apoptosis (PUMA), and Bim expression in human islets and rodent ?-cells...
  59. Jay D, Mitchell D, Williams M. Bim mediates the elimination of functionally unfit Th1 responders from the memory pool. PLoS ONE. 2013;8:e67363 pubmed publisher
    ..transition from effector to memory is accompanied by enhanced expression of the pro-apoptotic Bcl-2 family member Bim. Here, we show that Bim deficiency enables the survival of poorly functional Th1 responders that are normally ..
  60. Doonan F, Donovan M, Gomez Vicente V, Bouillet P, Cotter T. Bim expression indicates the pathway to retinal cell death in development and degeneration. J Neurosci. 2007;27:10887-94 pubmed
    ..The purpose of this study was to investigate a possible role for Bim, in retinal development and degeneration, upstream of Bax and Bak...
  61. Wojciechowski S, Tripathi P, Bourdeau T, Acero L, Grimes H, Katz J, et al. Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis. J Exp Med. 2007;204:1665-75 pubmed
    We examined the role of the antiapoptotic molecule Bcl-2 in combating the proapoptotic molecule Bim in control of naive and memory T cell homeostasis using Bcl-2(-/-) mice that were additionally deficient in one or both alleles of Bim...
  62. Bouillet P, Zhang L, Huang D, Webb G, Bottema C, Shore P, et al. Gene structure alternative splicing, and chromosomal localization of pro-apoptotic Bcl-2 relative Bim. Mamm Genome. 2001;12:163-8 pubmed
    b>Bim is a proapoptotic protein of the Bcl-2 family that shares only the short BH3 domain with other members. It has three isoforms, apparently produced by alternative splicing...
  63. O CONNOR L, Strasser A, O Reilly L, Hausmann G, Adams J, Cory S, et al. Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J. 1998;17:384-95 pubmed
    ..An expression screen for proteins that bind to Bcl-2 yielded a small novel protein, denoted Bim, whose only similarity to any known protein is the short (nine amino acid) BH3 motif shared by most Bcl-2 ..
  64. Redmond W, Wei C, Kreuwel H, Sherman L. The apoptotic pathway contributing to the deletion of naive CD8 T cells during the induction of peripheral tolerance to a cross-presented self-antigen. J Immunol. 2008;180:5275-82 pubmed
    ..death pathway that could be inhibited by overexpression of Bcl-2 or targeted deletion of the proapoptotic molecule, Bim, thereby resulting in accumulation of activated clone 4 T cells...
  65. Ramjaun A, Tomlinson S, Eddaoudi A, Downward J. Upregulation of two BH3-only proteins, Bmf and Bim, during TGF beta-induced apoptosis. Oncogene. 2007;26:970-81 pubmed
    ..Gene expression analysis identified the proapoptotic Bcl-2 family members, Bmf and Bim, as induced by TGFbeta, dependent on both Smad4 and p38 function and the generation of reactive oxygen species...
  66. 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
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