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Gene Review

Bax  -  BCL2-associated X protein

Mus musculus

Synonyms: Apoptosis regulator BAX
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Disease relevance of Bax

  • Bax inactivation also improved postnatal growth rate and myofiber histology and decreased fixed contractures of Lama2(-/-) mice [1].
  • Taken together, these results provide unprecedented evidence that the membrane-associated anti-apoptotic CD19-Lyn complex may be at least as important as Bcl-2/Bax ratio for survival of lymphoma cells [2].
  • We previously showed that overexpression of Bax restores the chemosensitivity of Bax-deficient breast cancer cell lines [3].
  • Adenovirus E1B 19-kDa death suppressor protein interacts with Bax but not with Bad [4].
  • Using murine lung endothelial cells as a model, we found that the induction of apoptosis by hypoxia/reoxygenation involved the activation of both Bax-dependent and death receptor-mediated pathways [5].

High impact information on Bax

  • Although its ability to activate various p53 target genes is largely compromised, the p53(QS) protein retains the ability to transactivate the gene Bax [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].
  • Thus, Ahr-driven Bax transcription is a novel and evolutionarily conserved cell-death signaling pathway responsible for environmental toxicant-induced ovarian failure [8].
  • Oocytes in human ovarian biopsies grafted into immunodeficient mice also accumulate Bax and undergo apoptosis after PAH exposure in vivo [8].
  • Mice lacking either Ahr or the pro-apoptotic protein Bax have an increased number of primordial follicles, and these mutant oocytes are resistant to PAH toxicity [9].

Chemical compound and disease context of Bax


Biological context of Bax


Anatomical context of Bax


Associations of Bax with chemical compounds

  • Peptide mass fingerprinting identified this protein as Bid, a BH3 domain-containing protein known to interact with both Bcl2 and Bax [22].
  • Thus, in young mice, Bax emerges as an essential protein in the death pathway induced by IL-7 deficiency [23].
  • One potential target of JNK is Bax translocation, which was enhanced by APAP and blocked by the JNK inhibitor [24].
  • These data show that Bik/Nbk, which, unlike Bax, carries only a BH3 but no BH1 or BH2 domain may be a target to enhance chemosensitivity [3].
  • The levels of Bax and Bad proteins remained relatively constant during DMSO-induced differentiation [25].
  • Specific depletion of PKCzeta by RNA interference blocks nicotine-stimulated Bax phosphorylation and enhances apoptotic cell death [26].
  • The subcellular distribution of Proline 13 mutant Bax was identical to wild-type Bax in both healthy and apoptotic cells [27].

Physical interactions of Bax


Enzymatic interactions of Bax

  • However, Bax with BH3 deleted did not form heterodimers with Bcl-XL, but retained its ability to counter the death repressor activity of Bcl-XL [30].
  • Moreover, in the absence of the putative transmembrane C-terminal domain, Bax does not form ionic channels in the presence of cut Bid [31].

Regulatory relationships of Bax


Other interactions of Bax

  • Tumor-cell resistance to death receptor--induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax [37].
  • Thus, the function of either Bax or Bak appears required to initiate most forms of apoptosis and to suppress oncogenic transformation [18].
  • Consistent with this prediction, truncation of this short helix was required for Bim/Bax interaction and led to spontaneous activation of Bax [19].
  • Bax deficiency partially corrects interleukin-7 receptor alpha deficiency [23].
  • NGF withdrawal also results in elevation of a known p53 target, the apoptotic protein Bax [38].
  • They demonstrate that Bax, Bid, and MMP-12 play similar roles in bleomycin-induced fibrosis, thereby highlighting the importance of this Bid-activated, Bax-mediated pathway and downstream MMP-12 in a variety of fibrogenic settings [39].

Analytical, diagnostic and therapeutic context of Bax

  • Thus, Bax mutation in mismatch repair--deficient tumors can cause resistance to death receptor--targeted therapy, but pre-exposure to chemotherapy rescues tumor sensitivity [37].
  • Animal models suggest that Bax and Bak play an essential role in the implementation of apoptosis and as a result can hinder tumorigenesis [40].
  • However, whereas combination treatment applied to in vitro cell culture was characterized by a significant up-regulation and activation of Bax and down-regulation of Bcl-xL, the treatment applied to tumors induced Bak and Bcl-xS, whereas Bcl-omega and Bcl-xL were down-regulated [41].
  • Western blot analysis revealed that the expression of Bcl-xL, Bax, and Apaf-1 was not affected in cells transfected with sense or antisense AP-4 genes [42].
  • Furthermore, using immunocytochemistry as well as chemical blocking of putative apical pathways we could demonstrate that Bak is activated prior to Bax [43].


  1. Inhibition of apoptosis improves outcome in a model of congenital muscular dystrophy. Girgenrath, M., Dominov, J.A., Kostek, C.A., Miller, J.B. J. Clin. Invest. (2004) [Pubmed]
  2. Membrane-associated CD19-LYN complex is an endogenous p53-independent and Bc1-2-independent regulator of apoptosis in human B-lineage lymphoma cells. Myers, D.E., Jun, X., Waddick, K.G., Forsyth, C., Chelstrom, L.M., Gunther, R.L., Tumer, N.E., Bolen, J., Uckun, F.M. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Expression of the death gene Bik/Nbk promotes sensitivity to drug-induced apoptosis in corticosteroid-resistant T-cell lymphoma and prevents tumor growth in severe combined immunodeficient mice. Daniel, P.T., Pun, K.T., Ritschel, S., Sturm, I., Holler, J., Dörken, B., Brown, R. Blood (1999) [Pubmed]
  4. Adenovirus E1B 19-kDa death suppressor protein interacts with Bax but not with Bad. Chen, G., Branton, P.E., Yang, E., Korsmeyer, S.J., Shore, G.C. J. Biol. Chem. (1996) [Pubmed]
  5. Hepatocyte growth factor protects against hypoxia/reoxygenation-induced apoptosis in endothelial cells. Wang, X., Zhou, Y., Kim, H.P., Song, R., Zarnegar, R., Ryter, S.W., Choi, A.M. J. Biol. Chem. (2004) [Pubmed]
  6. The p53QS transactivation-deficient mutant shows stress-specific apoptotic activity and induces embryonic lethality. Johnson, T.M., Hammond, E.M., Giaccia, A., Attardi, L.D. Nat. Genet. (2005) [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. Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals. Matikainen, T., Perez, G.I., Jurisicova, A., Pru, J.K., Schlezinger, J.J., Ryu, H.Y., Laine, J., Sakai, T., Korsmeyer, S.J., Casper, R.F., Sherr, D.H., Tilly, J.L. Nat. Genet. (2001) [Pubmed]
  9. Eggs in the balance. Matzuk, M.M. Nat. Genet. (2001) [Pubmed]
  10. 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]
  11. Resistance of pancreatic cancer to gemcitabine treatment is dependent on mitochondria-mediated apoptosis. Schniewind, B., Christgen, M., Kurdow, R., Haye, S., Kremer, B., Kalthoff, H., Ungefroren, H. Int. J. Cancer (2004) [Pubmed]
  12. Bleomycin induces alveolar epithelial cell death through JNK-dependent activation of the mitochondrial death pathway. Lee, V.Y., Schroedl, C., Brunelle, J.K., Buccellato, L.J., Akinci, O.I., Kaneto, H., Snyder, C., Eisenbart, J., Budinger, G.R., Chandel, N.S. Am. J. Physiol. Lung Cell Mol. Physiol. (2005) [Pubmed]
  13. Genistein-induced apoptosis of p815 mastocytoma cells is mediated by Bax and augmented by a proteasome inhibitor, lactacystin. Park, B.S., Baek, S.J., Song, K.H., Kim, K.H., Jeong, S.J., Jeong, M.H., Seo, S.Y., Lee, S.W., Yoo, K.S., Yoo, Y.H. Nutrition and cancer. (2002) [Pubmed]
  14. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Yang, E., Zha, J., Jockel, J., Boise, L.H., Thompson, C.B., Korsmeyer, S.J. Cell (1995) [Pubmed]
  15. Integral role of Noxa in p53-mediated apoptotic response. Shibue, T., Takeda, K., Oda, E., Tanaka, H., Murasawa, H., Takaoka, A., Morishita, Y., Akira, S., Taniguchi, T., Tanaka, N. Genes Dev. (2003) [Pubmed]
  16. Deficiency in Bak and Bax perturbs thymic selection and lymphoid homeostasis. Rathmell, J.C., Lindsten, T., Zong, W.X., Cinalli, R.M., Thompson, C.B. Nat. Immunol. (2002) [Pubmed]
  17. 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]
  18. 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]
  19. The structure of a Bcl-xL/Bim fragment complex: implications for Bim function. Liu, X., Dai, S., Zhu, Y., Marrack, P., Kappler, J.W. Immunity (2003) [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. Apoptosis regulation in tetraploid cancer cells. Castedo, M., Coquelle, A., Vivet, S., Vitale, I., Kauffmann, A., Dessen, P., Pequignot, M.O., Casares, N., Valent, A., Mouhamad, S., Schmitt, E., Modjtahedi, N., Vainchenker, W., Zitvogel, L., Lazar, V., Garrido, C., Kroemer, G. EMBO J. (2006) [Pubmed]
  22. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Luo, X., Budihardjo, I., Zou, H., Slaughter, C., Wang, X. Cell (1998) [Pubmed]
  23. Bax deficiency partially corrects interleukin-7 receptor alpha deficiency. Khaled, A.R., Li, W.Q., Huang, J., Fry, T.J., Khaled, A.S., Mackall, C.L., Muegge, K., Young, H.A., Durum, S.K. Immunity (2002) [Pubmed]
  24. c-Jun N-terminal kinase plays a major role in murine acetaminophen hepatotoxicity. Gunawan, B.K., Liu, Z.X., Han, D., Hanawa, N., Gaarde, W.A., Kaplowitz, N. Gastroenterology (2006) [Pubmed]
  25. Bcl-XL induction during terminal differentiation of friend erythroleukaemia cells correlates with delay of apoptosis and loss of proliferative capacity but not with haemoglobinization. Hafid-Medheb, K., Poindessous-Jazat, V., Augery-Bourget, Y., Hanania, N., Robert-Lézénès, J. Cell Death Differ. (1999) [Pubmed]
  26. Protein kinase Czeta abrogates the proapoptotic function of Bax through phosphorylation. Xin, M., Gao, F., May, W.S., Flagg, T., Deng, X. J. Biol. Chem. (2007) [Pubmed]
  27. The N-terminal conformation of Bax regulates cell commitment to apoptosis. Upton, J.P., Valentijn, A.J., Zhang, L., Gilmore, A.P. Cell Death Differ. (2007) [Pubmed]
  28. The Gfi-1 protooncoprotein represses Bax expression and inhibits T-cell death. Grimes, H.L., Gilks, C.B., Chan, T.O., Porter, S., Tsichlis, P.N. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  29. 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]
  30. Bax can antagonize Bcl-XL during etoposide and cisplatin-induced cell death independently of its heterodimerization with Bcl-XL. Simonian, P.L., Grillot, D.A., Merino, R., Nuñez, G. J. Biol. Chem. (1996) [Pubmed]
  31. Bid induces cytochrome c-impermeable Bax channels in liposomes. Roucou, X., Rostovtseva, T., Montessuit, S., Martinou, J.C., Antonsson, B. Biochem. J. (2002) [Pubmed]
  32. Apoptosis-inducing factor is involved in the regulation of caspase-independent neuronal cell death. Cregan, S.P., Fortin, A., MacLaurin, J.G., Callaghan, S.M., Cecconi, F., Yu, S.W., Dawson, T.M., Dawson, V.L., Park, D.S., Kroemer, G., Slack, R.S. J. Cell Biol. (2002) [Pubmed]
  33. Jak3 selectively regulates Bax and Bcl-2 expression to promote T-cell development. Wen, R., Wang, D., McKay, C., Bunting, K.D., Marine, J.C., Vanin, E.F., Zambetti, G.P., Korsmeyer, S.J., Ihle, J.N., Cleveland, J.L. Mol. Cell. Biol. (2001) [Pubmed]
  34. 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]
  35. Mammalian prion protein suppresses Bax-induced cell death in yeast. Li, A., Harris, D.A. J. Biol. Chem. (2005) [Pubmed]
  36. Required roles of Bax and JNKs in central and peripheral nervous system death of retinoblastoma-deficient mice. Keramaris, E., Ruzhynsky, V.A., Callaghan, S.M., Wong, E., Davis, R.J., Flavell, R., Slack, R.S., Park, D.S. J. Biol. Chem. (2008) [Pubmed]
  37. Tumor-cell resistance to death receptor--induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. LeBlanc, H., Lawrence, D., Varfolomeev, E., Totpal, K., Morlan, J., Schow, P., Fong, S., Schwall, R., Sinicropi, D., Ashkenazi, A. Nat. Med. (2002) [Pubmed]
  38. p53 is essential for developmental neuron death as regulated by the TrkA and p75 neurotrophin receptors. Aloyz, R.S., Bamji, S.X., Pozniak, C.D., Toma, J.G., Atwal, J., Kaplan, D.R., Miller, F.D. J. Cell Biol. (1998) [Pubmed]
  39. Transforming growth factor (TGF)-beta1 stimulates pulmonary fibrosis and inflammation via a Bax-dependent, bid-activated pathway that involves matrix metalloproteinase-12. Kang, H.R., Cho, S.J., Lee, C.G., Homer, R.J., Elias, J.A. J. Biol. Chem. (2007) [Pubmed]
  40. 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]
  41. 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]
  42. Regulation of the expression of caspase-9 by the transcription factor activator protein-4 in glucocorticoid-induced apoptosis. Tsujimoto, K., Ono, T., Sato, M., Nishida, T., Oguma, T., Tadakuma, T. J. Biol. Chem. (2005) [Pubmed]
  43. 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]
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