BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytesPhilippe Bouillet
The Walter and Eliza Hall Institute of Medical Research, Melbourne, P O The Royal Melbourne Hospital, Victoria 3050, Australia
Nature 415:922-6. 2002
..TCR ligation upregulated Bim expression and promoted interaction of Bim with Bcl-XL, inhibiting its survival function. These findings identify Bim as an essential initiator of apoptosis in thymocyte-negative selection...
- Role of Bim and other Bcl-2 family members in autoimmune and degenerative diseases
Peter Hughes
Walter and Eliza Hall Institute of Medical Research, Parkville, Vic, Australia
Curr Dir Autoimmun 9:74-94. 2006
..This chapter focuses on the role of Bim in the development and function of the immune system and its potential role in autoimmunity. Degenerative disorders due to increased apoptosis mediated by Bim are also discussed...
- Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak
Simon N Willis
Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
Science 315:856-9. 2007
..Our results indicate that BH3-only proteins induce apoptosis at least primarily by engaging the multiple pro-survival relatives guarding Bax and Bak...
- BH3-only proteins - evolutionarily conserved proapoptotic Bcl-2 family members essential for initiating programmed cell death
Philippe Bouillet
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
J Cell Sci 115:1567-74. 2002
..In response, they unleash the apoptotic cascade by inactivating the protective function of the pro-survival members of the Bcl-2 family and by activating the Bax/Bax-like pro-apoptotic family members...
Glucose induces pancreatic islet cell apoptosis that requires the BH3-only proteins Bim and Puma and multi-BH domain protein BaxMark D McKenzie
St Vincent s Institute, Melbourne, Australia
Diabetes 59:644-52. 2010
..We investigated the apoptotic pathway induced in mouse pancreatic islet cells after exposure to high concentrations of the reducing sugars ribose and glucose as a model of beta-cell death due to long-term metabolic stress...
- The BH3-only proteins Bim and Puma cooperate to impose deletional tolerance of organ-specific antigens
Daniel H D Gray
Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia
Immunity 37:451-62. 2012
..Our data show that Puma cooperates with Bim to impose a thymic-deletion checkpoint to peripheral self-antigens and cement the notion that defects in apoptosis alone are sufficient to cause autoimmune disease...
- Bcl-2, Bcl-x(L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells
Delphine Merino
The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
Blood 119:5807-16. 2012
..These results have profound implications for how BH3-mimetics induce apoptosis and how the use of these compounds can be optimized for treating lymphoid malignancies...
- Negative selection of semimature CD4(+)8(-)HSA+ thymocytes requires the BH3-only protein Bim but is independent of death receptor signaling
Andreas Villunger
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
Proc Natl Acad Sci U S A 101:7052-7. 2004
..These results reveal the mechanisms of apoptosis in negative selection of semimature thymocytes and have implications for immunological tolerance and autoimmunity...
- Concomitant loss of proapoptotic BH3-only Bcl-2 antagonists Bik and Bim arrests spermatogenesis
Leigh Coultas
The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
EMBO J 24:3963-73. 2005
..Thus, Bik and Bim share, upstream of Bax, the role of eliminating supernumerary germ cells during the first wave of spermatogenesis, a process vital for normal testicular development...
- Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity
Peter D Hughes
Molecular Genetics of Cancer, The Walter and Eliza Hall Institute of Medical Research, Melbourne 3050, Australia
Immunity 28:197-205. 2008
..These results identify critical overlapping roles for Fas and Bim in T cell death in immune response shutdown and prevention of immunopathology and thereby resolve a long-standing controversy...
- The role of BH3-only protein Bim extends beyond inhibiting Bcl-2-like prosurvival proteins
Delphine Merino
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia
J Cell Biol 186:355-62. 2009
..Thus, initiation of apoptosis in vivo appears to require features of both models...
- Destruction of tumor vasculature and abated tumor growth upon VEGF blockade is driven by proapoptotic protein Bim in endothelial cells
Edwina Naik
The Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria 3052, Australia
J Exp Med 208:1351-8. 2011
..They also indicate that drugs mimicking BH3-only proteins may be exploited to kill tumor cells not only directly but also indirectly by ablating the tumor vasculature...
Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cellsAnselm Enders
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
J Exp Med 198:1119-26. 2003
..Mechanistically, we determined that BCR ligation promoted interaction of Bim with Bcl-2, inhibiting its survival function. These findings demonstrate that Bim is a critical player in BCR-mediated apoptosis and in B lymphocyte deletion...
- Fatal hepatitis mediated by tumor necrosis factor TNFalpha requires caspase-8 and involves the BH3-only proteins Bid and Bim
Thomas Kaufmann
The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia
Immunity 30:56-66. 2009
..These observations identify caspase-8 and the BH3-only proteins Bid and Bim as potential therapeutic targets for treatment of inflammatory liver diseases...
- What do we know about the mechanisms of elimination of autoreactive T and B cells and what challenges remain
Andreas Strasser
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Immunol Cell Biol 86:57-66. 2008
..Finally, we speculate on the processes that may lead to the activation of Bim when antigen receptors are activated on autoreactive T or B cells...
- Loss of Bim increases T cell production and function in interleukin 7 receptor-deficient mice
Marc Pellegrini
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
J Exp Med 200:1189-95. 2004
..This indicates that pharmacological inhibition of Bim function might be useful for boosting immune responses in immunodeficient patients...
- Essential role for the BH3-only protein Bim but redundant roles for Bax, Bcl-2, and Bcl-w in the control of granulocyte survival
Andreas Villunger
Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Blood 101:2393-400. 2003
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- Proapoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody-forming cells
Silke F Fischer
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Blood 110:3978-84. 2007
..We have identified for the first time the physiologic mechanisms for killing low-affinity antibody-expressing B cells in an immune response and have shown this to be dependent on the BH3-only protein Bim...
- A novel BH3 ligand that selectively targets Mcl-1 reveals that apoptosis can proceed without Mcl-1 degradation
Erinna F Lee
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia
J Cell Biol 180:341-55. 2008
..Our data have important implications for the discovery of compounds that might kill cells whose survival depends on Mcl-1...
- Fas-mediated neutrophil apoptosis is accelerated by Bid, Bak, and Bax and inhibited by Bcl-2 and Mcl-1
Ben A Croker
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia
Proc Natl Acad Sci U S A 108:13135-40. 2011
..These data demonstrate that the intrinsic apoptosis pathway directly controls the kinetics of Fas-triggered apoptosis in neutrophils...
- Membrane-bound Fas ligand only is essential for Fas-induced apoptosis
Lorraine A O' Reilly
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia
Nature 461:659-63. 2009
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- Shutdown of an acute T cell immune response to viral infection is mediated by the proapoptotic Bcl-2 homology 3-only protein Bim
Marc Pellegrini
Division of Molecular Genetics of Cancer, The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Australia
Proc Natl Acad Sci U S A 100:14175-80. 2003
..These findings have implications for the therapeutic manipulation of immune responses to infections and immunization...
- XIAP discriminates between type I and type II FAS-induced apoptosis
Philipp J Jost
The Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3050, Australia
Nature 460:1035-9. 2009
..These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions...
- Hrk/DP5 contributes to the apoptosis of select neuronal populations but is dispensable for haematopoietic cell apoptosis
Leigh Coultas
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
J Cell Sci 120:2044-52. 2007
..These results demonstrate that HRK contributes to apoptosis signalling elicited by trophic factor withdrawal in certain neuronal populations but is dispensable for apoptosis of haematopoietic cells...
- Proapoptotic BH3-only Bcl-2 family member Bik/Blk/Nbk is expressed in hemopoietic and endothelial cells but is redundant for their programmed death
Leigh Coultas
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia
Mol Cell Biol 24:1570-81. 2004
..These results indicate that any function of Bik in programmed cell death and stress-induced apoptosis must overlap that of other BH3-only proteins...
- Peripheral deletion of autoreactive CD8 T cells by cross presentation of self-antigen occurs by a Bcl-2-inhibitable pathway mediated by Bim
Gayle M Davey
The Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Parkville 3050, Victoria, Australia
J Exp Med 196:947-55. 2002
..Bim-deficient T cells were not deleted in response to cross-presented self-antigen, strongly implicating Bim as the pro-apoptotic mediator of cross-tolerance...
- Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia
Stefan P Glaser
The Walter and Eliza Hall Institute, Parkville, Melbourne, Victoria 3052, Australia
Genes Dev 26:120-5. 2012
..Thus, targeting of Mcl-1 or regulators of its expression may be a useful strategy for the treatment of AML...
- Bim is a suppressor of Myc-induced mouse B cell leukemia
Alexander Egle
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria 3050, Australia
Proc Natl Acad Sci U S A 101:6164-9. 2004
..Whereas the p19Arf/p53 pathway is frequently mutated in tumors arising in Bim(+/+) Emicro-Myc mice, it was unaffected in most Bim-deficient tumors, indicating that Bim reduction is an effective alternative to loss of p53 function...
- Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic
Junya Kuroda
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia
Proc Natl Acad Sci U S A 103:14907-12. 2006
..These results demonstrate that Bim and Bad account for most, perhaps all, imatinib-induced killing of Bcr/Abl+ leukemic cells and suggest previously undescribed drug combination strategies for cancer therapy...
- Loss of pro-apoptotic BH3-only Bcl-2 family member Bim does not protect mutant Lurcher mice from neurodegeneration
Philippe Bouillet
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
J Neurosci Res 74:777-81. 2003
..Our studies show that Bim deficiency does not modify the Lurcher phenotype, ruling out an indispensable role for Bim in this neurodegenerative disease...
CD95, BIM and T cell homeostasisPhilippe Bouillet
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Nat Rev Immunol 9:514-9. 2009
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- ER stress triggers apoptosis by activating BH3-only protein Bim
Hamsa Puthalakath
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Cell 129:1337-49. 2007
..These results define the molecular mechanisms of ER stress-induced apoptosis and identify targets for therapeutic intervention in ER stress-related diseases...
- Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome
Vanessa S Marsden
The Walter and Eliza Hall Institute, Melbourne, 3050, Australia
Nature 419:634-7. 2002
..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...
- The control of apoptosis in lymphocyte selection
Andreas Strasser
Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria, Australia
Immunol Rev 193:82-92. 2003
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- The Bcl-2 family in autoimmune and degenerative disorders
Delphine Merino
Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute for Medical Research, Melbourne, Vic, Australia
Apoptosis 14:570-83. 2009
..The present review highlights the role of Bcl-2 family members in autoimmune and degenerative disorders, with a particular focus on the mouse models that have been used to study their function...
- BIM regulates apoptosis during mammary ductal morphogenesis, and its absence reveals alternative cell death mechanisms
Arnaud A Mailleux
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Dev Cell 12:221-34. 2007
..These data provide important mechanistic information on the processes involved in sculpting the mammary gland and demonstrate that BIM is a critical regulator of apoptosis in vivo...
- Bax and Bak: back-bone of T cell death
Philippe Bouillet
Nat Immunol 3:893-4. 2002
- Activated T cell death in vivo mediated by proapoptotic bcl-2 family member bim
David A Hildeman
Howard Hughes Medical Institute and Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA
Immunity 16:759-67. 2002
..Thus, the death of superantigen-stimulated T cells in vivo is mediated by Bim and may be modulated by a decrease in Bcl-2...
- Combined loss of proapoptotic genes Bak or Bax with Bim synergizes to cause defects in hematopoiesis and in thymocyte apoptosis
Jack Hutcheson
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St Louis, MO 63104, USA
J Exp Med 201:1949-60. 2005
..These data suggest an essential overlapping role for Bak or Bax and Bim in the intrinsic apoptotic pathway...
- Selective involvement of BH3-only Bcl-2 family members Bim and Bad in neonatal hypoxia-ischemia
Jayne M Ness
Department of Pediatrics, University of Alabama at Birmingham, 35487, USA
Brain Res 1099:150-9. 2006
..These results indicate that Bad and Bim are selectively involved in neuron death following neonatal HI and may be targets for therapeutic intervention...
- Two molecular pathways initiate mitochondria-dependent dopaminergic neurodegeneration in experimental Parkinson's disease
Celine Perier
Research Institute University Hospital Vall d Hebron, 08035 Barcelona, Spain
Proc Natl Acad Sci U S A 104:8161-6. 2007
..These results provide further insight into the pathogenesis of PD neurodegeneration and identify molecular targets of potential therapeutic significance for this disabling neurological illness...
- Bim expression indicates the pathway to retinal cell death in development and degeneration
Francesca Doonan
Tumour Biology Laboratory, Biochemistry Department, Bioscience Research Institute, University College Cork, Cork, Republic of Ireland
J Neurosci 27:10887-94. 2007
..However, the absence of BimEL expression correlates with caspase-independent death in the rd model...
- The RUNX3 tumor suppressor upregulates Bim in gastric epithelial cells undergoing transforming growth factor beta-induced apoptosis
Takashi Yano
Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore 138673, Singapore
Mol Cell Biol 26:4474-88. 2006
..These results demonstrate that RUNX3 is responsible for transcriptional up-regulation of Bim in TGF-beta-induced apoptosis...
- Adenosine A2A receptor-mediated cell death of mouse thymocytes involves adenylate cyclase and Bim and is negatively regulated by Nur77
Ildiko Kiss
Department of Biochemistry and Molecular Biology, Signaling and Apoptosis Research Group, Hungarian Academy of Sciences, Research Center of Molecular Medicine, University of Debrecen
Eur J Immunol 36:1559-71. 2006
..Collectively our data demonstrate that adenosine-induced cell death involves signaling pathways originally found in negative selection of thymocytes and suggest a determining role of Bim and a regulatory role for Nur77...
- MicroRNAs and lymphocyte homeostasis: dangerous eggs in a single basket
Delphine Merino
Molecular Genetics of Cancer Division, The Water and Eliza Hall Institute, Parkville, Victorial, Australia
Immunol Cell Biol 86:387-8. 2008
- Key roles of BIM-driven apoptosis in epithelial tumors and rational chemotherapy
Ting Ting Tan
Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08854, USA
Cancer Cell 7:227-38. 2005
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- NKT cell stimulation with glycolipid antigen in vivo: costimulation-dependent expansion, Bim-dependent contraction, and hyporesponsiveness to further antigenic challenge
Adam P Uldrich
Department Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia
J Immunol 175:3092-101. 2005
..In summary, this study significantly enhances our understanding of how NKT cells respond to primary and secondary antigenic challenge in vivo...
- Intrahepatic murine CD8 T-cell activation associates with a distinct phenotype leading to Bim-dependent death
Lauren E Holz
Centenary Institute, AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital and Faculty of Medicine, University of Sydney, Camperdown, New South Wales, Australia
Gastroenterology 135:989-97. 2008
..However, the molecular mechanism by which intrahepatically activated T cells become tolerant is unknown. Here, we investigated the phenotype and fate of naïve CD8 T cells activated by hepatocytes in vivo...
