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Gene Review

Bak1  -  BCL2-antagonist/killer 1

Mus musculus

Synonyms: Apoptosis regulator BAK, Bak, Bcl-2 homologous antagonist/killer, N-BAK1, N-Bak
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Disease relevance of Bak1


High impact information on Bak1

  • 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 [6].
  • The antagonistic balance between Bcl-x(L) and Bak constitutes a molecular clock that determines platelet life span: this represents an important paradigm for cellular homeostasis, and has profound implications for the diagnosis and treatment of disorders that affect platelet number and function [6].
  • However, using growth factor-dependent cells from Bax/Bak-deficient mice, we demonstrate that apoptosis is not essential to limit cell autonomous survival [7].
  • Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak [8].
  • The widespread tissue distribution of Bak messenger RNA, including those containing long-lived, terminally differentiated cell types, suggests that cell-death-inducing activity is broadly distributed, and that tissue-specific modulation of apoptosis is controlled primarily by regulation of molecules that inhibit apoptosis [8].

Biological context of Bak1

  • Thus, the function of either Bax or Bak appears required to initiate most forms of apoptosis and to suppress oncogenic transformation [9].
  • Combined loss of proapoptotic genes Bak or Bax with Bim synergizes to cause defects in hematopoiesis and in thymocyte apoptosis [10].
  • Bak and Bax are functionally redundant in non-neuronal cells and represent a mitochondrial convergence point for cell death signaling pathways [11].
  • N-Bak message and protein levels are elevated in cortical neurons in response to DNA damage, and subsequent induction of neuronal death is significantly delayed by expressing a full-length Bak antisense plasmid [11].
  • Furthermore, Bax and Bak deficiency dramatically increased E1A expression and virus replication [2].

Anatomical context of Bak1

  • Furthermore, whereas mouse embryo fibroblasts (MEF) expressing only Bax or Bak displayed resistance to transformation, bax(-/-)bak(-/-) MEF were nearly as prone to oncogenic transformation as p53(-/-) MEF [9].
  • Bak protein was present in early erythroblasts, but diminished progressively during differentiation [12].
  • N-Bak interacts with Bcl-XL but not BAX, suggesting an indirect mechanism for promoting Bax translocation to the mitochondria [11].
  • Overexpression of N-Bak promotes Bax translocation in HeLa cells and induces neuronal cell death in cortical, hippocampal, and cerebellar granule neurons in a Bax-dependent manner [11].
  • In the present study, we demonstrate that postnatal cortical and cerebellar granule neurons exclusively express an alternatively spliced, BH3 domain-only form of Bak (N-Bak), whereas astrocytes express only the full-length, multidomain form [11].

Associations of Bak1 with chemical compounds

  • These results suggest that neither activation of BH3-only proteins nor suppression of pro-survival Bcl-2 proteins is sufficient to kill cells in the absence of both Bax and Bak [9].
  • tBid interaction with cardiolipin primarily orchestrates mitochondrial dysfunctions and subsequently activates Bax and Bak [13].
  • N-Bak is generated by neuron-specific splicing of a novel 20-base pair exon, which changes the previously described Bak, containing Bcl-2 homology (BH) domains BH1, BH2, and BH3, into a shorter BH3-only protein [14].
  • Activation of Bak, Bax, and BH3-only proteins in the apoptotic response to doxorubicin [15].
  • In this study, we found that NPCs deficient in Apaf-1, or both the pro-apoptotic multidomain Bcl-2 family members Bax and Bak, were resistant to cytosine arabinoside and gamma-irradiation-induced apoptosis [16].

Physical interactions of Bak1

  • We demonstrate that antimycin A and a Bak BH3 peptide bind competitively to recombinant Bcl-2 [17].
  • Bak interacts with Mfn1 and Mfn2, two mitochondrial fusion proteins [18].

Regulatory relationships of Bak1


Other interactions of Bak1

  • The expression of the pro-apoptotic members Bax, Bak, Bid, and Bcl-x(S) was significantly ( P < 0.05) decreased after TPN [24].
  • These data suggest an essential overlapping role for Bak or Bax and Bim in the intrinsic apoptotic pathway [10].
  • While mutation of Bak had no effect, ablation of Bax suppressed the loss of Sertoli cells in Bclw mutants [25].
  • Bak was barely detectable and Bad protein level decreased in cells undergoing apoptosis [26].
  • Soy decreased Bak and increased COX-2 and ER-alpha expression site-specifically in female mice [27].

Analytical, diagnostic and therapeutic context of Bak1


  1. Caspase-2 triggers Bax-Bak-dependent and -independent cell death in colon cancer cells treated with resveratrol. Mohan, J., Gandhi, A.A., Bhavya, B.C., Rashmi, R., Karunagaran, D., Indu, R., Santhoshkumar, T.R. J. Biol. Chem. (2006) [Pubmed]
  2. Bak and Bax function to limit adenovirus replication through apoptosis induction. Cuconati, A., Degenhardt, K., Sundararajan, R., Anschel, A., White, E. J. Virol. (2002) [Pubmed]
  3. Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune disease. Takeuchi, O., Fisher, J., Suh, H., Harada, H., Malynn, B.A., Korsmeyer, S.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. Benzyl isothiocyanate-induced apoptosis in human breast cancer cells is initiated by reactive oxygen species and regulated by Bax and Bak. Xiao, D., Vogel, V., Singh, S.V. Mol. Cancer Ther. (2006) [Pubmed]
  5. Cytomegalovirus cell death suppressor vMIA blocks Bax- but not Bak-mediated apoptosis by binding and sequestering Bax at mitochondria. Arnoult, D., Bartle, L.M., Skaletskaya, A., Poncet, D., Zamzami, N., Park, P.U., Sharpe, J., Youle, R.J., Goldmacher, V.S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  6. Programmed anuclear cell death delimits platelet life span. Mason, K.D., Carpinelli, M.R., Fletcher, J.I., Collinge, J.E., Hilton, A.A., Ellis, S., Kelly, P.N., Ekert, P.G., Metcalf, D., Roberts, A.W., Huang, D.C., Kile, B.T. Cell (2007) [Pubmed]
  7. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Lum, J.J., Bauer, D.E., Kong, M., Harris, M.H., Li, C., Lindsten, T., Thompson, C.B. Cell (2005) [Pubmed]
  8. Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak. Kiefer, M.C., Brauer, M.J., Powers, V.C., Wu, J.J., Umansky, S.R., Tomei, L.D., Barr, P.J. Nature (1995) [Pubmed]
  9. BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Zong, W.X., Lindsten, T., Ross, A.J., MacGregor, G.R., Thompson, C.B. Genes Dev. (2001) [Pubmed]
  10. Combined loss of proapoptotic genes Bak or Bax with Bim synergizes to cause defects in hematopoiesis and in thymocyte apoptosis. Hutcheson, J., Scatizzi, J.C., Bickel, E., Brown, N.J., Bouillet, P., Strasser, A., Perlman, H. J. Exp. Med. (2005) [Pubmed]
  11. Neurons exclusively express N-Bak, a BH3 domain-only Bak isoform that promotes neuronal apoptosis. Uo, T., Kinoshita, Y., Morrison, R.S. J. Biol. Chem. (2005) [Pubmed]
  12. The roles of Bcl-X(L) and apopain in the control of erythropoiesis by erythropoietin. Gregoli, P.A., Bondurant, M.C. Blood (1997) [Pubmed]
  13. tBid interaction with cardiolipin primarily orchestrates mitochondrial dysfunctions and subsequently activates Bax and Bak. Gonzalvez, F., Pariselli, F., Dupaigne, P., Budihardjo, I., Lutter, M., Antonsson, B., Diolez, P., Manon, S., Martinou, J.C., Goubern, M., Wang, X., Bernard, S., Petit, P.X. Cell Death Differ. (2005) [Pubmed]
  14. Neuron-specific Bcl-2 homology 3 domain-only splice variant of Bak is anti-apoptotic in neurons, but pro-apoptotic in non-neuronal cells. Sun, Y.F., Yu, L.Y., Saarma, M., Timmusk, T., Arumae, U. J. Biol. Chem. (2001) [Pubmed]
  15. Activation of Bak, Bax, and BH3-only proteins in the apoptotic response to doxorubicin. Panaretakis, T., Pokrovskaja, K., Shoshan, M.C., Grandér, D. J. Biol. Chem. (2002) [Pubmed]
  16. Caspase regulation of genotoxin-induced neural precursor cell death. D'Sa, C., Klocke, B.J., Cecconi, F., Lindsten, T., Thompson, C.B., Korsmeyer, S.J., Flavell, R.A., Roth, K.A. J. Neurosci. Res. (2003) [Pubmed]
  17. Antimycin A mimics a cell-death-inducing Bcl-2 homology domain 3. Tzung, S.P., Kim, K.M., Basañez, G., Giedt, C.D., Simon, J., Zimmerberg, J., Zhang, K.Y., Hockenbery, D.M. Nat. Cell Biol. (2001) [Pubmed]
  18. Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins. Brooks, C., Wei, Q., Feng, L., Dong, G., Tao, Y., Mei, L., Xie, Z.J., Dong, Z. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  19. Bak but not Bax is essential for Bcl-xS-induced apoptosis. Lindenboim, L., Kringel, S., Braun, T., Borner, C., Stein, R. Cell Death Differ. (2005) [Pubmed]
  20. Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. Zong, W.X., Li, C., Hatzivassiliou, G., Lindsten, T., Yu, Q.C., Yuan, J., Thompson, C.B. J. Cell Biol. (2003) [Pubmed]
  21. Bax and Bak independently promote cytochrome C release from mitochondria. Degenhardt, K., Sundararajan, R., Lindsten, T., Thompson, C., White, E. J. Biol. Chem. (2002) [Pubmed]
  22. Mcl-1 down-regulation potentiates ABT-737 lethality by cooperatively inducing Bak activation and Bax translocation. Chen, S., Dai, Y., Harada, H., Dent, P., Grant, S. Cancer Res. (2007) [Pubmed]
  23. The effect of Bcl-2 adenovirus against murine hepatocyte apoptosis caused by tumor necrosis factor alpha and D-galactosamine. Zhang, B., Zhang, D., Ren, H., Ma, Y. Zhonghua Gan Zang Bing Za Zhi (2001) [Pubmed]
  24. Total parenteral nutrition-induced apoptosis in mouse intestinal epithelium: regulation by the Bcl-2 protein family. Wildhaber, B.E., Lynn, K.N., Yang, H., Teitelbaum, D.H. Pediatr. Surg. Int. (2002) [Pubmed]
  25. BCLW mediates survival of postmitotic Sertoli cells by regulating BAX activity. Ross, A.J., Amy, S.P., Mahar, P.L., Lindsten, T., Knudson, C.M., Thompson, C.B., Korsmeyer, S.J., MacGregor, G.R. Dev. Biol. (2001) [Pubmed]
  26. v-Abl protein tyrosine kinase (PTK) mediated suppression of apoptosis is associated with the up-regulation of Bcl-XL. Chen, Q., Turner, J., Watson, A.J., Dive, C. Oncogene (1997) [Pubmed]
  27. Gender-specific modulation of markers for premalignancy by nutritional soy and calcium in the mouse colon. Bises, G., Bajna, E., Manhardt, T., Gerdenitsch, W., Kallay, E., Cross, H.S. J. Nutr. (2007) [Pubmed]
  28. Nonredundant role of Bax and Bak in Bid-mediated apoptosis. Cartron, P.F., Juin, P., Oliver, L., Martin, S., Meflah, K., Vallette, F.M. Mol. Cell. Biol. (2003) [Pubmed]
  29. Apoptosis induction in prostate cancer cells and xenografts by combined treatment with Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand and CPT-11. Ray, S., Almasan, A. Cancer Res. (2003) [Pubmed]
  30. Early events of target deprivation/axotomy-induced neuronal apoptosis in vivo: oxidative stress, DNA damage, p53 phosphorylation and subcellular redistribution of death proteins. Martin, L.J., Price, A.C., McClendon, K.B., Al-Abdulla, N.A., Subramaniam, J.R., Wong, P.C., Liu, Z. J. Neurochem. (2003) [Pubmed]
  31. Humanin binds and nullifies Bid activity by blocking its activation of Bax and Bak. Zhai, D., Luciano, F., Zhu, X., Guo, B., Satterthwait, A.C., Reed, J.C. J. Biol. Chem. (2005) [Pubmed]
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