Bak1

Summary

Gene Symbol: Bak1
Description: BCL2-antagonist/killer 1
Alias: Bak, N-BAK1, N-Bak, bcl-2 homologous antagonist/killer, Bcl2 homologous antagonist/killer, apoptosis regulator BAK
Species: mouse
Products:     Bak1

Top Publications

  1. Lindsten T, Ross A, King A, Zong W, Rathmell J, Shiels H, et al. The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell. 2000;6:1389-99 pubmed
    ..However, mice lacking bax display limited phenotypic abnormalities. As presented here, bak(-/-) mice were found to be developmentally normal and reproductively fit and failed to develop any age-related ..
  2. Mizuta T, Shimizu S, Matsuoka Y, Nakagawa T, Tsujimoto Y. A Bax/Bak-independent mechanism of cytochrome c release. J Biol Chem. 2007;282:16623-30 pubmed
    Bax and Bak are multidomain pro-apoptotic members of the Bcl-2 family of proteins that regulate mitochondria-mediated apoptosis by direct modulation of mitochondrial membrane permeability...
  3. Degenhardt K, Sundararajan R, Lindsten T, Thompson C, White E. Bax and Bak independently promote cytochrome C release from mitochondria. J Biol Chem. 2002;277:14127-34 pubmed
    Pro-apoptotic Bax and Bak have been implicated in the regulation of p53-dependent apoptosis...
  4. Willis S, Chen L, Dewson G, Wei A, Naik E, Fletcher J, et al. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev. 2005;19:1294-305 pubmed
    ..proteins trigger apoptosis by binding via their BH3 domain to prosurvival relatives, while the proapoptotic Bax and Bak have an essential downstream role involving permeabilization of organellar membranes and induction of caspase ..
  5. Krajewska M, Mai J, Zapata J, Ashwell K, Schendel S, Reed J, et al. Dynamics of expression of apoptosis-regulatory proteins Bid, Bcl-2, Bcl-X, Bax and Bak during development of murine nervous system. Cell Death Differ. 2002;9:145-57 pubmed
    ..and immunoblotting to examine the expression of Bid and four other Bcl-2 family proteins (Bcl-2, Bcl-X, Bax and Bak) in the developing and adult murine central nervous system (CNS)...
  6. Kirsch D, Dinulescu D, Miller J, Grimm J, Santiago P, Young N, et al. A spatially and temporally restricted mouse model of soft tissue sarcoma. Nat Med. 2007;13:992-7 pubmed
    ..Deletion of the Ink4a-Arf locus (Cdkn2a), but not Bak1 and Bax, could substitute for mutation of Trp53 in this model...
  7. Chittenden T, Flemington C, Houghton A, Ebb R, Gallo G, Elangovan B, et al. A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions. EMBO J. 1995;14:5589-96 pubmed
    ..The Bcl-2 homolog, Bak, promotes apoptosis and binds anti-apoptotic family members including Bcl-2 and Bcl-xL...
  8. Brooks C, Wei Q, Feng L, Dong G, Tao Y, Mei L, et al. Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins. Proc Natl Acad Sci U S A. 2007;104:11649-54 pubmed
    ..Bax and Bak, two multidomain Bcl-2 family proteins, provide a requisite gateway to mitochondrial injury...
  9. Scorrano L, Oakes S, Opferman J, Cheng E, Sorcinelli M, Pozzan T, et al. BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science. 2003;300:135-9 pubmed
    BAX and BAK are "multidomain" proapoptotic proteins that initiate mitochondrial dysfunction but also localize to the endoplasmic reticulum (ER)...

More Information

Publications74

  1. Ulrich E, Kauffmann Zeh A, Hueber A, Williamson J, Chittenden T, Ma A, et al. Gene structure, cDNA sequence, and expression of murine Bak, a proapoptotic Bcl-2 family member. Genomics. 1997;44:195-200 pubmed
    To facilitate the creation of Bak knockout mice and the further analysis of this Bcl-2 family member, we have isolated and sequenced the complete mouse Bak cDNA...
  2. Llambi F, Moldoveanu T, Tait S, Bouchier Hayes L, Temirov J, McCormick L, et al. A unified model of mammalian BCL-2 protein family interactions at the mitochondria. Mol Cell. 2011;44:517-31 pubmed publisher
    ..of exogenous BH3 domains inserted into a tBID backbone that can activate the proapoptotic effectors BAX and BAK to permeabilize membranes without being universally sequestered by all antiapoptotic BCL-2 proteins...
  3. Duckworth C, Pritchard D. Suppression of apoptosis, crypt hyperplasia, and altered differentiation in the colonic epithelia of bak-null mice. Gastroenterology. 2009;136:943-52 pubmed publisher
    ..We have therefore investigated intestinal epithelial apoptosis in bak-null mice...
  4. Merino D, Khaw S, Glaser S, Anderson D, Belmont L, Wong C, et al. Bcl-2, Bcl-x(L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells. Blood. 2012;119:5807-16 pubmed publisher
    ..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...
  5. Kodama T, Hikita H, Kawaguchi T, Shigekawa M, Shimizu S, Hayashi Y, et al. Mcl-1 and Bcl-xL regulate Bak/Bax-dependent apoptosis of the megakaryocytic lineage at multistages. Cell Death Differ. 2012;19:1856-69 pubmed publisher
    ..All these phenotypes were fully restored if Bak and Bax, downstream apoptosis executioners, were also deficient...
  6. Upton J, Austgen K, Nishino M, Coakley K, Hagen A, Han D, et al. Caspase-2 cleavage of BID is a critical apoptotic signal downstream of endoplasmic reticulum stress. Mol Cell Biol. 2008;28:3943-51 pubmed publisher
    ..reticulum (ER) and triggers cell death through activation of the multidomain proapoptotic BCL-2 proteins BAX and BAK at the outer mitochondrial membrane...
  7. Cheng E, Sheiko T, Fisher J, Craigen W, Korsmeyer S. VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science. 2003;301:513-7 pubmed
    The multidomain proapoptotic molecules BAK or BAX are required to initiate the mitochondrial pathway of apoptosis...
  8. Ren D, Kim H, Tu H, Westergard T, Fisher J, Rubens J, et al. The VDAC2-BAK rheostat controls thymocyte survival. Sci Signal. 2009;2:ra48 pubmed publisher
    The proapoptotic proteins BAX and BAK constitute the mitochondrial apoptotic gateway that executes cellular demise after integrating death signals...
  9. Baines C, Kaiser R, Sheiko T, Craigen W, Molkentin J. Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol. 2007;9:550-5 pubmed
    ..These results indicate that Vdacs are dispensable for both MPT and Bcl-2 family member-driven cell death. ..
  10. Zong W, Li C, Hatzivassiliou G, Lindsten T, Yu Q, Yuan J, et al. Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. J Cell Biol. 2003;162:59-69 pubmed
    Bax and Bak play a redundant but essential role in apoptosis initiated by the mitochondrial release of apoptogenic factors. In addition to their presence at the mitochondrial outer membrane, Bax and Bak can also localize to the ER...
  11. Hsu S, Kaipia A, McGee E, Lomeli M, Hsueh A. Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members. Proc Natl Acad Sci U S A. 1997;94:12401-6 pubmed
    ..This finding is in direct contrast to the ability of other pro-apoptotic members (Bax, Bak, and Bik) to interact with all of the anti-apoptotic proteins...
  12. Dai H, Smith A, Meng X, Schneider P, Pang Y, Kaufmann S. Transient binding of an activator BH3 domain to the Bak BH3-binding groove initiates Bak oligomerization. J Cell Biol. 2011;194:39-48 pubmed publisher
    The mechanism by which the proapoptotic Bcl-2 family members Bax and Bak release cytochrome c from mitochondria is incompletely understood...
  13. Dowling M, Josefsson E, Henley K, Hodgkin P, Kile B. Platelet senescence is regulated by an internal timer, not damage inflicted by hits. Blood. 2010;116:1776-8 pubmed publisher
    ..Thus, at steady state, platelet senescence is probably the product of internal processes rather than external hits. ..
  14. Chipuk J, McStay G, Bharti A, Kuwana T, Clarke C, Siskind L, et al. Sphingolipid metabolism cooperates with BAK and BAX to promote the mitochondrial pathway of apoptosis. Cell. 2012;148:988-1000 pubmed publisher
    ..We observed that dissociation of heterotypic membranes from mitochondria inhibited BAK/BAX-dependent cytochrome c (cyto c) release...
  15. Jakobson M, Lintulahti A, Arumae U. mRNA for N-Bak, a neuron-specific BH3-only splice isoform of Bak, escapes nonsense-mediated decay and is translationally repressed in the neurons. Cell Death Dis. 2012;3:e269 pubmed publisher
    mRNA for neuronal Bak (N-Bak), a splice variant of pro-apoptotic Bcl-2 family member Bak is expressed in the neurons...
  16. Kodama T, Takehara T, Hikita H, Shimizu S, Shigekawa M, Li W, et al. BH3-only activator proteins Bid and Bim are dispensable for Bak/Bax-dependent thrombocyte apoptosis induced by Bcl-xL deficiency: molecular requisites for the mitochondrial pathway to apoptosis in platelets. J Biol Chem. 2011;286:13905-13 pubmed publisher
    A pivotal step in the mitochondrial pathway of apoptosis is activation of Bak and Bax, although the molecular mechanism remains controversial...
  17. Madesh M, Zong W, Hawkins B, Ramasamy S, Venkatachalam T, Mukhopadhyay P, et al. Execution of superoxide-induced cell death by the proapoptotic Bcl-2-related proteins Bid and Bak. Mol Cell Biol. 2009;29:3099-112 pubmed publisher
    ..and mitochondrial membrane potential loss that is not dependent upon H(2)O(2) and divalent cations and requires Bak in a Bax-independent fashion...
  18. Hetz C, Bernasconi P, Fisher J, Lee A, Bassik M, Antonsson B, et al. Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha. Science. 2006;312:572-6 pubmed
    ..We investigated UPR signaling events in mice in the absence of the proapoptotic BCL-2 family members BAX and BAK [double knockout (DKO)]...
  19. Lindsten T, Golden J, Zong W, Minarcik J, Harris M, Thompson C. The proapoptotic activities of Bax and Bak limit the size of the neural stem cell pool. J Neurosci. 2003;23:11112-9 pubmed
    The proapoptotic Bcl-2 family members Bak and Bax play central and redundant roles in the regulation of apoptosis. In this study, we investigated the effect of loss of Bax and Bak in the CNS...
  20. 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
    ..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. ..
  21. Cartron P, Juin P, Oliver L, Martin S, Meflah K, Vallette F. Nonredundant role of Bax and Bak in Bid-mediated apoptosis. Mol Cell Biol. 2003;23:4701-12 pubmed
    Animal models suggest that Bax and Bak play an essential role in the implementation of apoptosis and as a result can hinder tumorigenesis. We analyzed the expression of these proteins in 50 human glioblastoma multiforme (GBM) tumors...
  22. Gross A, McDonnell J, Korsmeyer S. BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 1999;13:1899-911 pubmed
  23. Dunkle A, Dzhagalov I, He Y. Mcl-1 promotes survival of thymocytes by inhibition of Bak in a pathway separate from Bcl-2. Cell Death Differ. 2010;17:994-1002 pubmed publisher
    ..By generation of various genetic mouse models, we found that Mcl-1-deficient thymocytes die largely by a Bak-specific mechanism...
  24. Lum J, Bauer D, Kong M, Harris M, Li C, Lindsten T, et al. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell. 2005;120:237-48 pubmed
    ..However, using growth factor-dependent cells from Bax/Bak-deficient mice, we demonstrate that apoptosis is not essential to limit cell autonomous survival...
  25. Chittenden T, Harrington E, O CONNOR R, Flemington C, Lutz R, Evan G, et al. Induction of apoptosis by the Bcl-2 homologue Bak. Nature. 1995;374:733-6 pubmed
    ..Here we describe the complementary DNA cloning and functional analysis of a new Bcl-2 homologue, Bak, which promotes cell death and counteracts the protection from apoptosis provided by Bcl-2...
  26. Smits C, Czabotar P, Hinds M, Day C. Structural plasticity underpins promiscuous binding of the prosurvival protein A1. Structure. 2008;16:818-29 pubmed publisher
    ..this study, crystal structures of complexes between the prosurvival protein A1 and the BH3 domains from Puma, Bmf, Bak, and Bid have been solved...
  27. Waxman A, Kolliputi N. IL-6 protects against hyperoxia-induced mitochondrial damage via Bcl-2-induced Bak interactions with mitofusins. Am J Respir Cell Mol Biol. 2009;41:385-96 pubmed publisher
    ..Finally, Bcl-2 blocked the dissociation of Bak from mitofusin protein (Mfn) 2, and inhibited the interaction between Bak and Mfn1...
  28. Przemeck S, Duckworth C, Pritchard D. Radiation-induced gastric epithelial apoptosis occurs in the proliferative zone and is regulated by p53, bak, bax, and bcl-2. Am J Physiol Gastrointest Liver Physiol. 2007;292:G620-7 pubmed
    ..Decreased numbers of apoptotic gastric epithelial cells were observed in p53-null, bak-null, and bax-null mice compared with wild-type counterparts 6 and 48 h after 12 Gy gamma-radiation...
  29. Takahashi Y, Karbowski M, Yamaguchi H, Kazi A, Wu J, Sebti S, et al. Loss of Bif-1 suppresses Bax/Bak conformational change and mitochondrial apoptosis. Mol Cell Biol. 2005;25:9369-82 pubmed
    ..Here, we provide evidence that Bif-1 plays a regulatory role in apoptotic activation of not only Bax but also Bak and appears to be involved in suppression of tumorigenesis...
  30. Cam M, Handke W, Picard Maureau M, Brune W. Cytomegaloviruses inhibit Bak- and Bax-mediated apoptosis with two separate viral proteins. Cell Death Differ. 2010;17:655-65 pubmed publisher
    ..apoptosis by preventing activation and/or oligomerization of the proapoptotic mitochondrial proteins Bax and Bak. Here we show that cytomegaloviruses (CMVs) have adopted a different strategy...
  31. Reyes N, Fisher J, Austgen K, Vandenberg S, Huang E, Oakes S. Blocking the mitochondrial apoptotic pathway preserves motor neuron viability and function in a mouse model of amyotrophic lateral sclerosis. J Clin Invest. 2010;120:3673-9 pubmed publisher
    ..tissue-specific deletion in the mouse CNS of BCL2-associated X protein (BAX) and BCL2-homologous antagonist/killer (BAK), 2 proapoptotic BCL-2 family proteins that together represent an essential gateway to the mitochondrial apoptotic ..
  32. Sun Y, Yu L, Saarma M, Arumae U. Mutational analysis of N-Bak reveals different structural requirements for antiapoptotic activity in neurons and proapoptotic activity in nonneuronal cells. Mol Cell Neurosci. 2003;23:134-43 pubmed
    N-Bak, a neuron-specific BH3-only splice variant of Bak, is proapoptotic when overexpressed in nonneuronal cells, but antiapoptotic in NGF-deprived sympathetic neurons...
  33. Cleland M, Norris K, Karbowski M, Wang C, Suen D, Jiao S, et al. Bcl-2 family interaction with the mitochondrial morphogenesis machinery. Cell Death Differ. 2011;18:235-47 pubmed publisher
    ..Here we report that Bax and Bak participate in the regulation of mitochondrial fusion in mouse embryonic fibroblasts, primary mouse neurons and ..
  34. Rathmell J, Lindsten T, Zong W, Cinalli R, Thompson C. Deficiency in Bak and Bax perturbs thymic selection and lymphoid homeostasis. Nat Immunol. 2002;3:932-9 pubmed
    b>Bak and Bax are required and redundant regulators of an intrinsic mitochondrial cell death pathway. To analyze this pathway in T cell development and homeostasis, we reconstituted mice with Bak(-/-)Bax<(-/-) hematopoietic cells...
  35. 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. ..
  36. Brunelle J, Santore M, Budinger G, Tang Y, Barrett T, Zong W, et al. c-Myc sensitization to oxygen deprivation-induced cell death is dependent on Bax/Bak, but is independent of p53 and hypoxia-inducible factor-1. J Biol Chem. 2004;279:4305-12 pubmed
    ..Our results demonstrate that murine embryonic fibroblasts from bax-/-bak-/- mice that conditionally express c-Myc did not die in response to either oxygen or serum deprivation...
  37. Putcha G, Harris C, Moulder K, Easton R, Thompson C, Johnson E. Intrinsic and extrinsic pathway signaling during neuronal apoptosis: lessons from the analysis of mutant mice. J Cell Biol. 2002;157:441-53 pubmed
    ..proteins did not, however, exhibit functional redundancy or compensatory expression, at least in the Bax-/-, Bak-/-, Bim-/-, Bid-/-, and Bad-/- neurons examined...
  38. Ren D, Tu H, Kim H, Wang G, Bean G, Takeuchi O, et al. BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program. Science. 2010;330:1390-3 pubmed publisher
    Although the proteins BAX and BAK are required for initiation of apoptosis at the mitochondria, how BAX and BAK are activated remains unsettled...
  39. 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
    While activation of BAX/BAK by BH3-only molecules (BH3s) is essential for mitochondrial apoptosis, the underlying mechanisms remain unsettled...
  40. Oh K, Singh P, Lee K, Foss K, Lee S, Park M, et al. Conformational changes in BAK, a pore-forming proapoptotic Bcl-2 family member, upon membrane insertion and direct evidence for the existence of BH3-BH3 contact interface in BAK homo-oligomers. J Biol Chem. 2010;285:28924-37 pubmed publisher
    During apoptosis, the pro-apoptotic Bcl-2 family proteins BAK and BAX form large oligomeric pores in the mitochondrial outer membrane...
  41. Sun Y, Yu L, Saarma M, Timmusk T, Arumae U. Neuron-specific Bcl-2 homology 3 domain-only splice variant of Bak is anti-apoptotic in neurons, but pro-apoptotic in non-neuronal cells. J Biol Chem. 2001;276:16240-7 pubmed
    We have identified and characterized N-Bak, a neuron-specific isoform of the pro-apoptotic Bcl-2 family member Bak...
  42. Kirsch D, Santiago P, di Tomaso E, Sullivan J, Hou W, Dayton T, et al. p53 controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis. Science. 2010;327:593-6 pubmed publisher
    ..Studying mouse models, we found that selective deletion of the proapoptotic genes Bak1 and Bax from the GI epithelium or from endothelial cells did not protect mice from developing the GI syndrome after ..
  43. Martinez Caballero S, Dejean L, Kinnally M, Oh K, Mannella C, Kinnally K. Assembly of the mitochondrial apoptosis-induced channel, MAC. J Biol Chem. 2009;284:12235-45 pubmed publisher
    ..clamp studies of mitochondria isolated from cells deficient in one or both of the pro-apoptotic proteins Bax and Bak show that at least one of the proteins must be present for formation of the cytochrome c-translocating channel, ..
  44. Dansen T, Whitfield J, Rostker F, Brown Swigart L, Evan G. Specific requirement for Bax, not Bak, in Myc-induced apoptosis and tumor suppression in vivo. J Biol Chem. 2006;281:10890-5 pubmed
    Bax and Bak comprise the mitochondrial gateway for apoptosis induced by diverse stimuli...
  45. Mason K, Carpinelli M, Fletcher J, Collinge J, Hilton A, Ellis S, et al. Programmed anuclear cell death delimits platelet life span. Cell. 2007;128:1173-86 pubmed
    ..Pro-survival Bcl-x(L) constrains the pro-apoptotic activity of Bak to maintain platelet survival, but as Bcl-x(L) degrades, aged platelets are primed for cell death...
  46. Valentijn A, Upton J, Bates N, Gilmore A. Bax targeting to mitochondria occurs via both tail anchor-dependent and -independent mechanisms. Cell Death Differ. 2008;15:1243-54 pubmed publisher
    Bax is a member of the Bcl-2 family that, together with Bak, is required for permeabilisation of the outer mitochondrial membrane (OMM)...
  47. Takeuchi O, Fisher J, Suh H, Harada H, Malynn B, Korsmeyer S. Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune disease. Proc Natl Acad Sci U S A. 2005;102:11272-7 pubmed
    ..Here we show proapoptotic BCL-2 family members BAX and BAK are essential for regulating the number of B cells at both immature and mature developmental stages...
  48. Mason K, Lin A, Robb L, Josefsson E, Henley K, Gray D, et al. Proapoptotic Bak and Bax guard against fatal systemic and organ-specific autoimmune disease. Proc Natl Acad Sci U S A. 2013;110:2599-604 pubmed publisher
    ..b>Bak and Bax are two proapoptotic members of the Bcl-2 protein family with overlapping, essential roles in the intrinsic ..
  49. Taylor J, Quilty D, Banadyga L, Barry M. The vaccinia virus protein F1L interacts with Bim and inhibits activation of the pro-apoptotic protein Bax. J Biol Chem. 2006;281:39728-39 pubmed
    ..We previously showed that F1L interacts with the pro-apoptotic Bcl-2 family member Bak and inhibits activation of Bak following an apoptotic stimulus (Wasilenko, S. T., Banadyga, L., Bond, D...
  50. Josefsson E, James C, Henley K, Debrincat M, Rogers K, Dowling M, et al. Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets. J Exp Med. 2011;208:2017-31 pubmed publisher
    ..we generated mice with hematopoietic- or megakaryocyte-specific deletions of the essential mediators of apoptosis, Bak and Bax. We found that platelet production was unperturbed...
  51. Dewson G, Kratina T, Sim H, Puthalakath H, Adams J, Colman P, et al. To trigger apoptosis, Bak exposes its BH3 domain and homodimerizes via BH3:groove interactions. Mol Cell. 2008;30:369-80 pubmed publisher
    The Bcl-2 relative Bak is thought to drive apoptosis by forming homo-oligomers that permeabilize mitochondria, but how it is activated and oligomerizes is unclear...
  52. Irrinki K, Mallilankaraman K, Thapa R, Chandramoorthy H, Smith F, Jog N, et al. Requirement of FADD, NEMO, and BAX/BAK for aberrant mitochondrial function in tumor necrosis factor alpha-induced necrosis. Mol Cell Biol. 2011;31:3745-58 pubmed publisher
    ..Finally, elimination of BAX and BAK or overexpression of Bcl-x(L) protects cells from necroptosis at a later step...
  53. Whelan R, Konstantinidis K, Wei A, Chen Y, Reyna D, Jha S, et al. Bax regulates primary necrosis through mitochondrial dynamics. Proc Natl Acad Sci U S A. 2012;109:6566-71 pubmed publisher
    ..Bcl-2 proteins Bax and Bak are the principal activators of MOMP and apoptosis...
  54. Schoenwaelder S, Yuan Y, Josefsson E, White M, Yao Y, Mason K, et al. Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function. Blood. 2009;114:663-6 pubmed publisher
    ..To clarify this, we investigated the consequence of removing the essential mediators of apoptosis, Bak and Bax, or directly inducing apoptosis with the BH3 mimetic compound ABT-737...
  55. Fannjiang Y, Kim C, Huganir R, Zou S, Lindsten T, Thompson C, et al. BAK alters neuronal excitability and can switch from anti- to pro-death function during postnatal development. Dev Cell. 2003;4:575-85 pubmed
    b>BAK is a pro-apoptotic BCL-2 family protein that localizes to mitochondria...
  56. Uo T, Kinoshita Y, Morrison R. Neurons exclusively express N-Bak, a BH3 domain-only Bak isoform that promotes neuronal apoptosis. J Biol Chem. 2005;280:9065-73 pubmed
    b>Bak is generally recognized as a multidomain, pro-apoptotic member of the Bcl-2 family. Bak and Bax are functionally redundant in non-neuronal cells and represent a mitochondrial convergence point for cell death signaling pathways...
  57. Wei M, Lindsten T, Mootha V, Weiler S, Gross A, Ashiya M, et al. tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev. 2000;14:2060-71 pubmed
    ..b>Bak-deficient mitochondria and blocking antibodies reveal tBID binds to its mitochondrial partner BAK to release ..
  58. Ekert P, Jabbour A, Manoharan A, Heraud J, Yu J, Pakusch M, et al. Cell death provoked by loss of interleukin-3 signaling is independent of Bad, Bim, and PI3 kinase, but depends in part on Puma. Blood. 2006;108:1461-8 pubmed
    ..IL-3-dependent cell lines from mice lacking the genes for Bad, Bim, Puma, both Bad and Bim, and both Bax and Bak. Surprisingly, Bad was not required for cell death following IL-3 withdrawal, suggesting changes to phosphorylation ..
  59. Alavian K, Li H, Collis L, Bonanni L, Zeng L, Sacchetti S, et al. Bcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase. Nat Cell Biol. 2011;13:1224-33 pubmed publisher
    ..Our findings indicate that increased mitochondrial efficiency contributes to the enhanced synaptic efficacy found in Bcl-x(L)-expressing neurons. ..
  60. Lindenboim L, Kringel S, Braun T, Borner C, Stein R. Bak but not Bax is essential for Bcl-xS-induced apoptosis. Cell Death Differ. 2005;12:713-23 pubmed
    ..fibroblasts derived from mice deficient in the multidomain proapoptotic members of the Bcl-2 family (Bax and Bak) and the apoptotic components of the apoptosome (Apaf-1 and caspase-9) to unravel the cascade of events by which ..
  61. Du H, Wolf J, Schafer B, Moldoveanu T, Chipuk J, Kuwana T. BH3 domains other than Bim and Bid can directly activate Bax/Bak. J Biol Chem. 2011;286:491-501 pubmed publisher
    ..of a subgroup of the Bcl-2 family, known as the BH3-only proteins, activate pro-apoptotic effectors (Bax and Bak) to initiate MOMP. They do so by neutralizing pro-survival Bcl-2 proteins and/or directly activating Bax/Bak...
  62. Rucker E, Dierisseau P, Wagner K, Garrett L, Wynshaw Boris A, Flaws J, et al. Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis. Mol Endocrinol. 2000;14:1038-52 pubmed
    ..These findings demonstrate that the balance of Bcl-x and Bax control PGC survival and apoptosis. ..
  63. Dewson G, Kratina T, Czabotar P, Day C, Adams J, Kluck R. Bak activation for apoptosis involves oligomerization of dimers via their alpha6 helices. Mol Cell. 2009;36:696-703 pubmed publisher
    A pivotal step toward apoptosis is oligomerization of the Bcl-2 relative Bak. We recently reported that its oligomerization initiates by insertion of an exposed BH3 domain into the groove of another Bak monomer...
  64. Pietsch E, Perchiniak E, Canutescu A, Wang G, Dunbrack R, Murphy M. Oligomerization of BAK by p53 utilizes conserved residues of the p53 DNA binding domain. J Biol Chem. 2008;283:21294-304 pubmed publisher
    ..Using immunopurification protocols and mass spectrometry, we previously identified the proapoptotic protein BAK as a mitochondrial p53-binding protein and showed that recombinant p53 directly binds to BAK and can induce its ..
  65. Majewski N, Nogueira V, Bhaskar P, Coy P, Skeen J, Gottlob K, et al. Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol Cell. 2004;16:819-30 pubmed
    ..of hexokinase from mitochondria potently induce cytochrome c release and apoptosis, even in the absence of Bax and Bak. These effects are inhibited by activated Akt, but not by Bcl-2, implying that changes in outer mitochondrial ..