Bim

Summary

Gene Symbol: Bim
Description: BCL2 like 11
Alias: BAM, BIM, BOD, bcl-2-like protein 11, BCL2-like 11 (apoptosis facilitator), bcl-2 interacting mediator of cell death, bcl-2 interacting protein Bim, bcl-2-related ovarian death agonist
Species: human
Products:     Bim

Top Publications

  1. Puthalakath H, Huang D, O Reilly L, King S, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell. 1999;3:287-96 pubmed
    ..We examined the regulation of the proapoptotic activity of the BH3-only protein Bim. In healthy cells, most Bim molecules were bound to LC8 cytoplasmic dynein light chain and thereby sequestered to ..
  2. Herrant M, Jacquel A, Marchetti S, Belhacene N, Colosetti P, Luciano F, et al. Cleavage of Mcl-1 by caspases impaired its ability to counteract Bim-induced apoptosis. Oncogene. 2004;23:7863-73 pubmed
    ..with alpha-Tubulin near the internal face of the plasma membrane, while Mcl-1 Delta127 coassociated with Bim-EL at the mitochondrial level...
  3. 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. ..
  4. 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
    ..quot;multidomain" BAX, BAK demonstrate long-term resistance to all BH3 domain-only members, including BAD, BIM, and NOXA...
  5. Kazi A, Sun J, Doi K, Sung S, Takahashi Y, Yin H, et al. The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax- and Bim-dependent manner. J Biol Chem. 2011;286:9382-92 pubmed publisher
    ..Bcl-X(L), and Mcl-1, which bind to the BH3 ?-helical domain of pro-apoptotic proteins such as Bax, Bak, Bad, and Bim, and inhibit their function...
  6. Cartlidge R, Thomas G, Cagnol S, Jong K, Molton S, Finch A, et al. Oncogenic BRAF(V600E) inhibits BIM expression to promote melanoma cell survival. Pigment Cell Melanoma Res. 2008;21:534-44 pubmed publisher
    ..Here we demonstrate that expression of BIM, a pro-apoptotic member of the BCL-2 family, is inhibited by BRAF-->MEK-->ERK signaling in mouse and human ..
  7. Cragg M, Jansen E, Cook M, Harris C, Strasser A, Scott C. Treatment of B-RAF mutant human tumor cells with a MEK inhibitor requires Bim and is enhanced by a BH3 mimetic. J Clin Invest. 2008;118:3651-9 pubmed publisher
    ..on upregulation and dephosphorylation of the proapoptotic, Bcl-2 homology 3-only (BH3-only) Bcl-2 family member Bim. However, upregulation of Bim was insufficient for extensive apoptosis and was countered by overexpression of Bcl-2...
  8. Wickenden J, Jin H, Johnson M, Gillings A, Newson C, Austin M, et al. Colorectal cancer cells with the BRAF(V600E) mutation are addicted to the ERK1/2 pathway for growth factor-independent survival and repression of BIM. Oncogene. 2008;27:7150-61 pubmed publisher
    ..embryonic fibroblasts from conditional knock-in transgenic mice activates ERK1/2, represses the BH3-only protein BIM and protects cells from growth factor withdrawal...
  9. Toh W, Nam S, Sabapathy K. An essential role for p73 in regulating mitotic cell death. Cell Death Differ. 2010;17:787-800 pubmed publisher
    ..the absence of p73 reduced mitotic death by compromising the expression of the proapoptotic BH3-only protein Bim and thereby affecting cytochrome c release and caspase activation...
  10. Matsui H, Shinjyo T, Inaba T. Structure of the human Bim gene and its transcriptional regulation in Baf-3, interleukin-3-dependent hematopoietic cells. Mol Biol Rep. 2005;32:79-85 pubmed
    ..studies have indicated that in Baf-3, interleukin (IL)-3-dependent cells, apoptosis is caused predominantly by Bim, a BH3-only cell death activator that belongs to the Bcl-2 superfamily...

Detail Information

Publications84

  1. Puthalakath H, Huang D, O Reilly L, King S, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell. 1999;3:287-96 pubmed
    ..We examined the regulation of the proapoptotic activity of the BH3-only protein Bim. In healthy cells, most Bim molecules were bound to LC8 cytoplasmic dynein light chain and thereby sequestered to ..
  2. Herrant M, Jacquel A, Marchetti S, Belhacene N, Colosetti P, Luciano F, et al. Cleavage of Mcl-1 by caspases impaired its ability to counteract Bim-induced apoptosis. Oncogene. 2004;23:7863-73 pubmed
    ..with alpha-Tubulin near the internal face of the plasma membrane, while Mcl-1 Delta127 coassociated with Bim-EL at the mitochondrial level...
  3. 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. ..
  4. 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
    ..quot;multidomain" BAX, BAK demonstrate long-term resistance to all BH3 domain-only members, including BAD, BIM, and NOXA...
  5. Kazi A, Sun J, Doi K, Sung S, Takahashi Y, Yin H, et al. The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax- and Bim-dependent manner. J Biol Chem. 2011;286:9382-92 pubmed publisher
    ..Bcl-X(L), and Mcl-1, which bind to the BH3 ?-helical domain of pro-apoptotic proteins such as Bax, Bak, Bad, and Bim, and inhibit their function...
  6. Cartlidge R, Thomas G, Cagnol S, Jong K, Molton S, Finch A, et al. Oncogenic BRAF(V600E) inhibits BIM expression to promote melanoma cell survival. Pigment Cell Melanoma Res. 2008;21:534-44 pubmed publisher
    ..Here we demonstrate that expression of BIM, a pro-apoptotic member of the BCL-2 family, is inhibited by BRAF-->MEK-->ERK signaling in mouse and human ..
  7. Cragg M, Jansen E, Cook M, Harris C, Strasser A, Scott C. Treatment of B-RAF mutant human tumor cells with a MEK inhibitor requires Bim and is enhanced by a BH3 mimetic. J Clin Invest. 2008;118:3651-9 pubmed publisher
    ..on upregulation and dephosphorylation of the proapoptotic, Bcl-2 homology 3-only (BH3-only) Bcl-2 family member Bim. However, upregulation of Bim was insufficient for extensive apoptosis and was countered by overexpression of Bcl-2...
  8. Wickenden J, Jin H, Johnson M, Gillings A, Newson C, Austin M, et al. Colorectal cancer cells with the BRAF(V600E) mutation are addicted to the ERK1/2 pathway for growth factor-independent survival and repression of BIM. Oncogene. 2008;27:7150-61 pubmed publisher
    ..embryonic fibroblasts from conditional knock-in transgenic mice activates ERK1/2, represses the BH3-only protein BIM and protects cells from growth factor withdrawal...
  9. Toh W, Nam S, Sabapathy K. An essential role for p73 in regulating mitotic cell death. Cell Death Differ. 2010;17:787-800 pubmed publisher
    ..the absence of p73 reduced mitotic death by compromising the expression of the proapoptotic BH3-only protein Bim and thereby affecting cytochrome c release and caspase activation...
  10. Matsui H, Shinjyo T, Inaba T. Structure of the human Bim gene and its transcriptional regulation in Baf-3, interleukin-3-dependent hematopoietic cells. Mol Biol Rep. 2005;32:79-85 pubmed
    ..studies have indicated that in Baf-3, interleukin (IL)-3-dependent cells, apoptosis is caused predominantly by Bim, a BH3-only cell death activator that belongs to the Bcl-2 superfamily...
  11. Nordigården A, Kraft M, Eliasson P, Labi V, Lam E, Villunger A, et al. BH3-only protein Bim more critical than Puma in tyrosine kinase inhibitor-induced apoptosis of human leukemic cells and transduced hematopoietic progenitors carrying oncogenic FLT3. Blood. 2009;113:2302-11 pubmed publisher
    ..Both compounds induced up-regulation of proapoptotic BH3-only proteins Bim and Puma, and subsequent cell death...
  12. 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.
  13. Aichberger K, Gleixner K, Mirkina I, Cerny Reiterer S, Peter B, Ferenc V, et al. Identification of proapoptotic Bim as a tumor suppressor in neoplastic mast cells: role of KIT D816V and effects of various targeted drugs. Blood. 2009;114:5342-51 pubmed publisher
    ..Recent data suggest that the proapoptotic BH3-only death regulator Bim plays a role as a tumor suppressor in various myeloid neoplasms...
  14. Will B, Siddiqi T, Jorda M, Shimamura T, Luptakova K, Staber P, et al. Apoptosis induced by JAK2 inhibition is mediated by Bim and enhanced by the BH3 mimetic ABT-737 in JAK2 mutant human erythroid cells. Blood. 2010;115:2901-9 pubmed publisher
    ..inhibition-induced apoptosis correlated with up-regulation of the nonphosphorylated form of the BH3-only protein Bim in hematopoietic cell lines bearing JAK2 mutations...
  15. Marani M, Tenev T, Hancock D, Downward J, Lemoine N. Identification of novel isoforms of the BH3 domain protein Bim which directly activate Bax to trigger apoptosis. Mol Cell Biol. 2002;22:3577-89 pubmed
    b>Bim (Bcl-2-interacting mediator of cell death) is a member of the BH3 domain-only subgroup of Bcl-2 family members, for which three splice variants have been described...
  16. Putcha G, Le S, Frank S, Besirli C, Clark K, Chu B, et al. JNK-mediated BIM phosphorylation potentiates BAX-dependent apoptosis. Neuron. 2003;38:899-914 pubmed
    ..N-terminal kinases (JNKs), culminating in coordinate AP1-dependent transactivation of the BH3-only BCL-2 proteins BIM(EL) and HRK, which in turn are critical for BAX-dependent cytochrome c release, caspase activation, and apoptosis...
  17. Kuwana T, Bouchier Hayes L, Chipuk J, Bonzon C, Sullivan B, Green D, et al. BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Mol Cell. 2005;17:525-35 pubmed
    ..Besides having this derepression function, the Bid and Bim peptides activated Bax directly and were the only BH3 peptides tested that could potently induce cytochrome c ..
  18. Rahmani M, Anderson A, Habibi J, Crabtree T, Mayo M, Harada H, et al. The BH3-only protein Bim plays a critical role in leukemia cell death triggered by concomitant inhibition of the PI3K/Akt and MEK/ERK1/2 pathways. Blood. 2009;114:4507-16 pubmed publisher
    ..These events were associated with pronounced Bim up-regulation, Mcl-1 down-regulation, marked Bak/Bax conformational change accompanied by Bax membrane ..
  19. Zhong Q, Gao W, Du F, Wang X. Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell. 2005;121:1085-95 pubmed
    ..Thus, Mule is a unique BH3-containing E3 ubiquitin ligase apical to Bcl-2 family proteins during DNA damage-induced apoptosis. ..
  20. Sharma G, Kar S, Palit S, Das P. 18?-glycyrrhetinic acid induces apoptosis through modulation of Akt/FOXO3a/Bim pathway in human breast cancer MCF-7 cells. J Cell Physiol. 2012;227:1923-31 pubmed publisher
    ..induced an increase in Bax:Bcl-2 ratio along with a significant increase in the protein level of the BH3 protein Bim. SiRNA-mediated knock down of Bim markedly attenuated GRA-mediated apoptosis...
  21. Jiang Z, Zheng X, Lytle R, Higashikubo R, Rich K. Lovastatin-induced up-regulation of the BH3-only protein, Bim, and cell death in glioblastoma cells. J Neurochem. 2004;89:168-78 pubmed
    ..Lovastatin-induced death occurs in correlation with significantly increased levels of the BH3-only protein, Bim. The up-regulation of Bim levels was directly associated with an increased incidence of apoptosis...
  22. 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...
  23. Stankiewicz A, Livingstone A, Mohseni N, Mosser D. Regulation of heat-induced apoptosis by Mcl-1 degradation and its inhibition by Hsp70. Cell Death Differ. 2009;16:638-47 pubmed publisher
    ..Our results demonstrate that loss of Mcl-1 is a critical heat-sensitive step leading to Bax activation that is controlled by Hsp70. ..
  24. Lopes A, Kellam P, Das A, Dunn C, Kwan A, Turner J, et al. Bim-mediated deletion of antigen-specific CD8 T cells in patients unable to control HBV infection. J Clin Invest. 2008;118:1835-45 pubmed publisher
    ..Further analysis confirmed that levels of the proapoptotic protein Bcl2-interacting mediator (Bim) were upregulated in HBV-specific CD8(+) T cells from patients with chronic HBV infection...
  25. Ewings K, Hadfield Moorhouse K, Wiggins C, Wickenden J, Balmanno K, Gilley R, et al. ERK1/2-dependent phosphorylation of BimEL promotes its rapid dissociation from Mcl-1 and Bcl-xL. EMBO J. 2007;26:2856-67 pubmed
    The proapoptotic protein Bim is expressed de novo following withdrawal of serum survival factors...
  26. 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...
  27. Deng J, Shimamura T, Perera S, Carlson N, Cai D, Shapiro G, et al. Proapoptotic BH3-only BCL-2 family protein BIM connects death signaling from epidermal growth factor receptor inhibition to the mitochondrion. Cancer Res. 2007;67:11867-75 pubmed
    ..As this result implies, key death-signaling proteins of the BCL-2 family, including BIM, were found to be up-regulated after erlotinib treatment and intercepted by overexpressed BCL-2...
  28. Morales A, Kurtoglu M, Matulis S, Liu J, Siefker D, Gutman D, et al. Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/Bcl-2 in Mcl-1-expressing myeloma cells. Blood. 2011;118:1329-39 pubmed publisher
    ..Codependence is not predicted by the expression level of antiapoptotic proteins, rather through interactions with Bim. Consistent with these findings, acquired resistance to ABT-737 results in loss of codependence through ..
  29. Wei G, Margolin A, Haery L, Brown E, Cucolo L, Julian B, et al. Chemical genomics identifies small-molecule MCL1 repressors and BCL-xL as a predictor of MCL1 dependency. Cancer Cell. 2012;21:547-62 pubmed publisher
    ..A computational model, validated in vivo, indicated that high BCL-xL expression confers resistance to MCL1 repression, thereby identifying a patient-selection strategy for the clinical development of MCL1 inhibitors. ..
  30. Warr M, Acoca S, Liu Z, Germain M, Watson M, Blanchette M, et al. BH3-ligand regulates access of MCL-1 to its E3 ligase. FEBS Lett. 2005;579:5603-8 pubmed
    ..A competing BH3-ligand derived from Bim interacted with Mcl-1 and prevented its interaction with LASU1 in HeLa cells, causing elevation of the steady-state ..
  31. Reginato M, Mills K, Becker E, Lynch D, Bonni A, Muthuswamy S, et al. Bim regulation of lumen formation in cultured mammary epithelial acini is targeted by oncogenes. Mol Cell Biol. 2005;25:4591-601 pubmed
    ..We demonstrate that the proapoptotic protein Bim may selectively trigger apoptosis of the centrally localized acinar cells, leading to temporally controlled lumen ..
  32. Essafi A, Fernandez De Mattos S, Hassen Y, Soeiro I, Mufti G, Thomas N, et al. Direct transcriptional regulation of Bim by FoxO3a mediates STI571-induced apoptosis in Bcr-Abl-expressing cells. Oncogene. 2005;24:2317-29 pubmed
    ..cell lines as model systems to investigate the molecular mechanisms whereby STI571 and FoxO3a regulate Bim expression and apoptosis...
  33. Han J, Goldstein L, Gastman B, Rabinowich H. Interrelated roles for Mcl-1 and BIM in regulation of TRAIL-mediated mitochondrial apoptosis. J Biol Chem. 2006;281:10153-63 pubmed
    ..the mitochondrial outer membrane by a complex between the prosurvival Bcl-2 member, Mcl-1 and the BH3-only protein, Bim. Under non-apoptotic conditions, Bim is sequestered by Mcl-1...
  34. Nakagawa T, Takeuchi S, Yamada T, Ebi H, Sano T, Nanjo S, et al. EGFR-TKI resistance due to BIM polymorphism can be circumvented in combination with HDAC inhibition. Cancer Res. 2013;73:2428-34 pubmed publisher
    b>BIM (BCL2L11) is a BH3-only proapoptotic member of the Bcl-2 protein family...
  35. Chen L, Willis S, Wei A, Smith B, Fletcher J, Hinds M, et al. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell. 2005;17:393-403 pubmed
    ..b>Bim and Puma potently engaged all the prosurvival proteins comparably...
  36. 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...
  37. López Royuela N, Balsas P, Galán Malo P, Anel A, Marzo I, Naval J. Bim is the key mediator of glucocorticoid-induced apoptosis and of its potentiation by rapamycin in human myeloma cells. Biochim Biophys Acta. 2010;1803:311-22 pubmed publisher
    ..Apoptotic gene expression profiling showed an increase in mRNA levels of Bim in MM.1S cells after Dex treatment and further increases in both cell lines when co-treated with rapamycin...
  38. Biswas S, Shi Y, Vonsattel J, Leung C, Troy C, Greene L. Bim is elevated in Alzheimer's disease neurons and is required for beta-amyloid-induced neuronal apoptosis. J Neurosci. 2007;27:893-900 pubmed
    ..implicated in the pathophysiology of AD, induces the proapoptotic protein Bcl-2 interacting mediator of cell death (Bim) in cultured hippocampal and cortical neurons...
  39. Ghosh A, Klocke B, Ballestas M, Roth K. CHOP potentially co-operates with FOXO3a in neuronal cells to regulate PUMA and BIM expression in response to ER stress. PLoS ONE. 2012;7:e39586 pubmed publisher
    ..PUMA (p53 upregulated modulator of apoptosis) and BIM (BCL2 interacting mediator of cell death), pro-apoptotic BH3 domain-only, BCL2 family members, have previously been ..
  40. Hagenbuchner J, Kuznetsov A, Hermann M, Hausott B, Obexer P, Ausserlechner M. FOXO3-induced reactive oxygen species are regulated by BCL2L11 (Bim) and SESN3. J Cell Sci. 2012;125:1191-203 pubmed publisher
    ..elevation of cellular ROS depends on FOXO3 activation and induction of its transcriptional target BCL2L11 (Bim)...
  41. Paterson A, Mockridge C, Adams J, Krysov S, Potter K, Duncombe A, et al. Mechanisms and clinical significance of BIM phosphorylation in chronic lymphocytic leukemia. Blood. 2012;119:1726-36 pubmed publisher
    ..In this study, we investigated the regulation of BIM, a proapoptotic BCL2-related protein, which is tightly regulated by phosphorylation...
  42. Nogueira T, Paula F, Villate O, Colli M, Moura R, Cunha D, et al. GLIS3, a susceptibility gene for type 1 and type 2 diabetes, modulates pancreatic beta cell apoptosis via regulation of a splice variant of the BH3-only protein Bim. PLoS Genet. 2013;9:e1003532 pubmed publisher
    ..apoptosis following GLIS3 KD indicated modulation of alternative splicing of the pro-apoptotic BH3-only protein Bim, favouring expression of the pro-death variant BimS via inhibition of the splicing factor SRp55...
  43. Gavathiotis E, Suzuki M, Davis M, Pitter K, Bird G, Katz S, et al. BAX activation is initiated at a novel interaction site. Nature. 2008;455:1076-81 pubmed publisher
    ..Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti-..
  44. Kvansakul M, Yang H, Fairlie W, Czabotar P, Fischer S, Perugini M, et al. Vaccinia virus anti-apoptotic F1L is a novel Bcl-2-like domain-swapped dimer that binds a highly selective subset of BH3-containing death ligands. Cell Death Differ. 2008;15:1564-71 pubmed publisher
    ..reveal an atypical BH3-binding profile, with sub-micromolar affinity only for the BH3 peptide of pro-apoptotic Bim and low micromolar affinity for the BH3 peptides of Bak and Bax...
  45. Morales A, Gutman D, Lee K, Boise L. BH3-only proteins Noxa, Bmf, and Bim are necessary for arsenic trioxide-induced cell death in myeloma. Blood. 2008;111:5152-62 pubmed publisher
    ..Coimmunoprecipitation demonstrated that Noxa and Puma bind Mcl-1 to release Bak and Bim within 6 hours of ATO addition. Bak and Bim are also released from Bcl-X(L)...
  46. Woods N, Yamaguchi H, Lee F, Bhalla K, Wang H. Anoikis, initiated by Mcl-1 degradation and Bim induction, is deregulated during oncogenesis. Cancer Res. 2007;67:10744-52 pubmed
    ..Using wild-type and c-Src-transformed NIH3T3 cells as a model, we identified Mcl-1 degradation and Bim up-regulation as a critical determinant of anoikis initiation...
  47. Fire E, Gulla S, Grant R, Keating A. Mcl-1-Bim complexes accommodate surprising point mutations via minor structural changes. Protein Sci. 2010;19:507-19 pubmed publisher
    ..We report the crystal structure of human Mcl-1 bound to a BH3 peptide derived from human Bim and the structures for three complexes that accommodate large physicochemical changes at conserved Bim sites...
  48. 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...
  49. Liu J, Chandra D, Tang S, Chopra D, Tang D. Identification and characterization of Bimgamma, a novel proapoptotic BH3-only splice variant of Bim. Cancer Res. 2002;62:2976-81 pubmed
    ..In this study, a novel human BH3-only protein, Bcl-2-interacting mediator (Bim)gamma, was identified during our study of regulation of prostate cancer cell death by Bcl-2 family proteins...
  50. U M, Miyashita T, Shikama Y, Tadokoro K, Yamada M. Molecular cloning and characterization of six novel isoforms of human Bim, a member of the proapoptotic Bcl-2 family. FEBS Lett. 2001;509:135-41 pubmed
    b>Bim protein is one of the BH3-only proteins, members of the Bcl-2 family that have only one of the Bcl-2 homology regions, BH3. BH3-only proteins are essential initiators of apoptotic cell death...
  51. Tan J, Zhuang L, Jiang X, Yang K, Karuturi K, Yu Q. Apoptosis signal-regulating kinase 1 is a direct target of E2F1 and contributes to histone deacetylase inhibitor-induced apoptosis through positive feedback regulation of E2F1 apoptotic activity. J Biol Chem. 2006;281:10508-15 pubmed
    ..We have previously shown that histone deacetylase inhibitors (HDACIs) activate the E2F1-Bim apoptotic pathway, leading to efficient cell killing in cancer cells with deregulated E2F1 activity...
  52. Howie H, Shiflett S, So M. Extracellular signal-regulated kinase activation by Neisseria gonorrhoeae downregulates epithelial cell proapoptotic proteins Bad and Bim. Infect Immun. 2008;76:2715-21 pubmed publisher
    ..Activated ERK specifically targeted two proapoptotic Bcl-2 homology domain 3 (BH3)-only proteins, Bim and Bad, for downregulation at the protein level. Bim downregulation occurred through the proteasome...
  53. Bean G, Ganesan Y, Dong Y, Takeda S, Liu H, Chan P, et al. PUMA and BIM are required for oncogene inactivation-induced apoptosis. Sci Signal. 2013;6:ra20 pubmed publisher
    ..quot; We demonstrate that PUMA and BIM are the key apoptotic effectors of tyrosine kinase inhibitors in breast cancers with amplification of the gene ..
  54. Konopleva M, Contractor R, Tsao T, Samudio I, Ruvolo P, Kitada S, et al. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell. 2006;10:375-88 pubmed
    ..ABT-737 induced the disruption of the BCL-2/BAX complex and BAK-dependent but BIM-independent activation of the intrinsic apoptotic pathway...
  55. Sandalova E, Wei C, Masucci M, Levitsky V. Regulation of expression of Bcl-2 protein family member Bim by T cell receptor triggering. Proc Natl Acad Sci U S A. 2004;101:3011-6 pubmed
    b>Bim, a proapoptotic BH3-only member of the Bcl-2 protein family, is required for central and peripheral deletion of T lymphocytes. Mechanisms regulating Bim activity in T cells remain poorly understood...
  56. Chen D, Zhou Q. Caspase cleavage of BimEL triggers a positive feedback amplification of apoptotic signaling. Proc Natl Acad Sci U S A. 2004;101:1235-40 pubmed
    ..One BH3-only protein, Bim, is the major physiological antagonist of the prosurvival proteins in B and T lymphocytes...
  57. Whelan K, Caldwell S, Shahriari K, Jackson S, Franchetti L, Johannes G, et al. Hypoxia suppression of Bim and Bmf blocks anoikis and luminal clearing during mammary morphogenesis. Mol Biol Cell. 2010;21:3829-37 pubmed publisher
    ..Here, we show that hypoxic conditions inhibit anoikis and block expression of proapoptotic BH3-only family members Bim and Bmf in epithelial cells...
  58. Sunters A, Fernandez De Mattos S, Stahl M, Brosens J, Zoumpoulidou G, Saunders C, et al. FoxO3a transcriptional regulation of Bim controls apoptosis in paclitaxel-treated breast cancer cell lines. J Biol Chem. 2003;278:49795-805 pubmed
    ..cancer cell lines expression of FoxO1a and FoxO3a correlated with the expression of the pro-apoptotic FoxO target Bim, which was associated with paclitaxel-induced apoptosis...
  59. Luciano F, Jacquel A, Colosetti P, Herrant M, Cagnol S, Pages G, et al. Phosphorylation of Bim-EL by Erk1/2 on serine 69 promotes its degradation via the proteasome pathway and regulates its proapoptotic function. Oncogene. 2003;22:6785-93 pubmed
    b>Bim is a proapoptotic member of the Bcl-2 family that shares only the BH3 domain with this family. Three Bim proteins Bim-EL, Bim-L and Bim-S are synthesized from the same transcript...
  60. Deng J, Carlson N, Takeyama K, Dal Cin P, Shipp M, Letai A. BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents. Cancer Cell. 2007;12:171-85 pubmed
    ..BCL-2 dependence correlates with high levels of proapoptotic BIM sequestered by BCL-2...
  61. Bouillet P, Purton J, Godfrey D, Zhang L, Coultas L, Puthalakath H, et al. BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes. Nature. 2002;415:922-6 pubmed
    ..We now report that thymocytes lacking the pro-apoptotic Bcl-2 family member Bim (also known as Bcl2l11) are refractory to apoptosis induced by TCR-CD3 stimulation...
  62. LaBelle J, Katz S, Bird G, Gavathiotis E, Stewart M, Lawrence C, et al. A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers. J Clin Invest. 2012;122:2018-31 pubmed publisher
    ..We harnessed the natural killing activity of BCL-2-interacting mediator of cell death (BIM), which contains one of the most potent BH3 death domains of the BCL-2 protein family, to restore BH3-dependent ..
  63. Wiggins C, Johnson M, Cook S. Refining the minimal sequence required for ERK1/2-dependent poly-ubiquitination and proteasome-dependent turnover of BIM. Cell Signal. 2010;22:801-8 pubmed publisher
    The pro-apoptotic protein BIM(EL) is phosphorylated by ERK1/2 and this targets the protein for poly-ubiquitination and degradation by the proteasome as a survival mechanism...
  64. Czabotar P, Westphal D, Dewson G, Ma S, Hockings C, Fairlie W, et al. Bax crystal structures reveal how BH3 domains activate Bax and nucleate its oligomerization to induce apoptosis. Cell. 2013;152:519-31 pubmed publisher
    ..A planar lipophilic surface on this homodimer may engage the membrane. Our results thus define critical Bax transitions toward apoptosis. ..
  65. Obexer P, Geiger K, Ambros P, Meister B, Ausserlechner M. FKHRL1-mediated expression of Noxa and Bim induces apoptosis via the mitochondria in neuroblastoma cells. Cell Death Differ. 2007;14:534-47 pubmed
    ..FKHRL1 induced TRAIL and the BH3-only proteins Noxa and Bim, implicating both extrinsic and intrinsic death pathways...
  66. Lei K, Davis R. JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc Natl Acad Sci U S A. 2003;100:2432-7 pubmed
    ..Here, we demonstrate that JNK phosphorylates two members of the BH3-only subgroup of Bcl2-related proteins (Bim and Bmf) that are normally sequestered by binding to dynein and myosin V motor complexes...
  67. Faber A, Corcoran R, Ebi H, Sequist L, Waltman B, Chung E, et al. BIM expression in treatment-naive cancers predicts responsiveness to kinase inhibitors. Cancer Discov. 2011;1:352-65 pubmed publisher
    ..Surprisingly, pretreatment RNA levels of the BH3-only pro-apoptotic BIM strongly predicted the capacity of EGFR, HER2, and PI3K inhibitors to induce apoptosis in EGFR-mutant, HER2-..
  68. Zha J, Harada H, Yang E, Jockel J, Korsmeyer S. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell. 1996;87:619-28 pubmed
    ..The rapid phosphorylation of BAD following IL-3 connects a proximal survival signal with the BCL-2 family, modulating this checkpoint for apoptosis. ..
  69. Santin I, Moore F, Colli M, Gurzov E, Marselli L, Marchetti P, et al. PTPN2, a candidate gene for type 1 diabetes, modulates pancreatic ?-cell apoptosis via regulation of the BH3-only protein Bim. Diabetes. 2011;60:3279-88 pubmed publisher
    ..Small interfering RNAs were used to inhibit PTPN2, STAT1, Bim, and Jun NH(2)-terminal kinase 1 (JNK1) expression...
  70. Reginato M, Mills K, Paulus J, Lynch D, Sgroi D, Debnath J, et al. Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis. Nat Cell Biol. 2003;5:733-40 pubmed
    ..Here, we identify the pro-apoptotic protein Bim as a critical mediator of anoikis in epithelial cells...
  71. 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
    ..Dependence on antiapoptotic proteins correlates with sequestration of activator BH3-only proteins like BID or BIM by antiapoptotic proteins...
  72. Sun H, Tsai A, Pan S, Ding Q, Yamaguchi H, Lin C, et al. EPOX inhibits angiogenesis by degradation of Mcl-1 through ERK inactivation. Clin Cancer Res. 2009;15:4904-14 pubmed publisher
    ..Down-regulation of Mcl-1 resulted in an increase in Mcl-1-free Bim, activation of Bax, and then signaling of mitochondria-mediated apoptosis...
  73. Zhang W, Cheng G, Gong J, Hermanto U, Zong C, Chan J, et al. RACK1 and CIS mediate the degradation of BimEL in cancer cells. J Biol Chem. 2008;283:16416-26 pubmed publisher
    ..Additionally, we demonstrated that RACK1 formed a complex with DLC1 and Bim, specifically BimEL, in the presence of apoptotic agents...
  74. Gong Y, Somwar R, Politi K, Balak M, Chmielecki J, Jiang X, et al. Induction of BIM is essential for apoptosis triggered by EGFR kinase inhibitors in mutant EGFR-dependent lung adenocarcinomas. PLoS Med. 2007;4:e294 pubmed
    ..The process requires induction of the proapoptotic BH3-only BCL2 family member BIM (i.e...
  75. Ley R, Ewings K, Hadfield K, Howes E, Balmanno K, Cook S. Extracellular signal-regulated kinases 1/2 are serum-stimulated "Bim(EL) kinases" that bind to the BH3-only protein Bim(EL) causing its phosphorylation and turnover. J Biol Chem. 2004;279:8837-47 pubmed
    b>Bim, a "BH3-only" protein, is expressed de novo following withdrawal of serum survival factors and promotes cell death...
  76. Mailleux A, Overholtzer M, Schmelzle T, Bouillet P, Strasser A, Brugge J. BIM regulates apoptosis during mammary ductal morphogenesis, and its absence reveals alternative cell death mechanisms. Dev Cell. 2007;12:221-34 pubmed
    ..Here, we demonstrate that disruption of the BH3-only proapoptotic factor Bim in mice prevents induction of apoptosis in and clearing of the lumen in terminal end buds during puberty...
  77. Matsui H, Asou H, Inaba T. Cytokines direct the regulation of Bim mRNA stability by heat-shock cognate protein 70. Mol Cell. 2007;25:99-112 pubmed
    Previous gene-targeting studies indicated that Bim, a BH3-only death activator, regulates total blood cell number. Cytokines contribute to this process by negatively regulating steady-state levels of Bim mRNA...
  78. Qi X, Wildey G, Howe P. Evidence that Ser87 of BimEL is phosphorylated by Akt and regulates BimEL apoptotic function. J Biol Chem. 2006;281:813-23 pubmed
    b>Bim, the Bcl-2 interacting mediator of cell death, is a member of the BH3-only family of pro-apoptotic proteins...
  79. Urbich C, Knau A, Fichtlscherer S, Walter D, Bruhl T, Potente M, et al. FOXO-dependent expression of the proapoptotic protein Bim: pivotal role for apoptosis signaling in endothelial progenitor cells. FASEB J. 2005;19:974-6 pubmed
    ..In addition, atorvastatin reduced the expression of the proapoptotic forkhead-regulated protein Bim in a PI3K-dependent manner...
  80. Gomez Bougie P, Bataille R, Amiot M. The imbalance between Bim and Mcl-1 expression controls the survival of human myeloma cells. Eur J Immunol. 2004;34:3156-64 pubmed
    ..In this study, we examined the regulation of the BH3-only protein Bim and its interaction with Mcl-1...