Bcl-2-associated X protein

BCL2-associated X protein

Available structures
PDB	1F16, 2G5B, 2K7W

Identifiers

Symbols

BAX; Bax zeta

External IDs

OMIM: 600040 MGI: 99702 HomoloGene: 7242 GeneCards: BAX Gene

Gene Ontology
Molecular function	• protein binding • lipid binding • channel activity • identical protein binding • protein homodimerization activity • protein homodimerization activity • protein heterodimerization activity • BH3 domain binding
Cellular component	• nucleus • cytoplasm • mitochondrion • mitochondrial outer membrane • mitochondrial outer membrane • mitochondrial permeability transition pore complex • endoplasmic reticulum • endoplasmic reticulum membrane • cytosol • cytosol • cytosol • membrane • pore complex
Biological process	• B cell apoptosis • release of cytochrome c from mitochondria • DNA fragmentation involved in apoptotic nuclear change • apoptosis • apoptosis • induction of apoptosis • induction of apoptosis • induction of apoptosis • activation of caspase activity • activation of caspase activity • cleavage of lamin • transformed cell apoptosis • mitochondrial fusion • induction of apoptosis by extracellular signals • induction of apoptosis by intracellular signals • induction of apoptosis by intracellular signals • activation of pro-apoptotic gene products • negative regulation of survival gene product expression • activation of caspase activity by cytochrome c • apoptotic mitochondrial changes • response to toxin • establishment or maintenance of transmembrane electrochemical gradient • nuclear fragmentation involved in apoptotic nuclear change • negative regulation of protein binding • release of matrix enzymes from mitochondria • regulation of apoptosis • regulation of protein homodimerization activity • regulation of protein heterodimerization activity • positive regulation of neuron apoptosis • mitochondrial fragmentation involved in apoptosis • induction of retinal programmed cell death • protein homooligomerization • regulation of mitochondrial membrane potential
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 19:
49.46 – 49.47 Mb

Chr 7:
52.72 – 52.72 Mb

PubMed search

[1]

[2]

The Bcl-2–associated X protein, or Bax is a protein of the Bcl-2 gene family. It promotes apoptosis by competing with Bcl-2 proper.

The BAX gene was the first identified pro-apoptotic member of the Bcl-2 protein family. ^[1] Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains (named BH1, BH2, BH3 and BH4), and can form hetero- or homodimers. Bcl-2 proteins act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. Orthologs of the BAX gene ^[2] have been identified in most mammals for which complete genome data are available.

Bax is a pro-apoptotic Bcl-2 protein containing BH1, BH2 and BH3 domains. In healthy mammalian cells, the majority of BAX is found in the cytosol, but upon initiation of apoptotic signaling, Bax undergoes a conformation shift, and inserts into organelle membranes, primarily the outer mitochondrial membrane.^[3] Bax is believed to interact with, and induce the opening of the mitochondrial voltage-dependent anion channel, VDAC. Alternatively, growing evidence suggest that activated Bax and/or Bak form an oligomeric pore, MAC in the outer membrane. This results in the release of cytochrome c and other pro-apoptotic factors from the mitochondria, often referred to as mitochondrial outer membrane permeabilization, leading to activation of caspases. This defines a direct role for Bax in mitochondrial outer membrane permeabilization, a role common to the Bcl-2 proteins containing the BH1, BH2 and BH3 domains.

The expression of BAX is upregulated by the tumor suppressor protein p53, and BAX has been shown to be involved in p53-mediated apoptosis. The p53 protein is a transcription factor that, when activated as part of the cell's response to stress, regulates many downstream target genes, including BAX. Wild-type p53 has been demonstrated to upregulate the transcription of a chimeric reporter plasmid utilizing the consensus promoter sequence of BAX approximately 50-fold over mutant p53. Thus it is likely that p53 promotes BAX's apoptotic faculties in vivo as a primary transcription factor. However, p53 also has a transcription-independent role in apoptosis. In particular, p53 interacts with Bax, promoting its activation as well as its insertion into the mitochondrial membrane.

1 Interactions
2 See also
3 References
4 Further reading

Interactions

Bcl-2-associated X protein has been shown to interact with SH3GLB1,^[4]^[5] VDAC1,^[6]^[7] BCL2-like 1,^[8]^[9]^[10] Bcl-2,^[11]^[12]^[13]^[14] SLC25A4,^[15] BCL2-related protein A1^[16] and YWHAQ.^[17]

References

^ Oltvai, Z. N.; Milliman, C. L. and Korsmeyer, S. J. (August 1993). "Bcl-2 Heterodimerizes In Vivo with a Conserved Homolog, Bax, That Accelerates Programed Cell Death". Cell 74 (4): 609–619. doi:10.1016/0092-8674(93)90509-O. PMID 8358790. http://www.cell.com/retrieve/pii/009286749390509O.
^ "OrthoMaM phylogenetic marker: BAX coding sequence". http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000087088_BAX.xml.
^ Wolter, K. G.; Hsu, Y., Smith, C. L., Mechushtan, A., Xi, X., and Youle, R. J. (December 1997). "Movement of BAX from Cytosol to Mitochondria during Apoptosis". Journal of Cell Biology 139 (5): 1281–1292. doi:10.1083/jcb.139.5.1281. PMC 2140220. PMID 9382873. http://www.jcb.org/cgi/content/full/139/5/1281.
^ Pierrat, B; Simonen M, Cueto M, Mestan J, Ferrigno P, Heim J (Jan. 2001). "SH3GLB, a new endophilin-related protein family featuring an SH3 domain". Genomics (United States) 71 (2): 222–34. doi:10.1006/geno.2000.6378. ISSN 0888-7543. PMID 11161816.
^ Cuddeback, S M; Yamaguchi H, Komatsu K, Miyashita T, Yamada M, Wu C, Singh S, Wang H G (Jun. 2001). "Molecular cloning and characterization of Bif-1. A novel Src homology 3 domain-containing protein that associates with Bax". J. Biol. Chem. (United States) 276 (23): 20559–65. doi:10.1074/jbc.M101527200. ISSN 0021-9258. PMID 11259440.
^ Weng, Changjiang; Li Yuan, Xu Dan, Shi Yong, Tang Hong (Mar. 2005). "Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells". J. Biol. Chem. (United States) 280 (11): 10491–500. doi:10.1074/jbc.M412819200. ISSN 0021-9258. PMID 15637055.
^ Shi, Yong; Chen Jianjun, Weng Changjiang, Chen Rui, Zheng Yanhua, Chen Quan, Tang Hong (Jun. 2003). "Identification of the protein-protein contact site and interaction mode of human VDAC1 with Bcl-2 family proteins". Biochem. Biophys. Res. Commun. (United States) 305 (4): 989–96. doi:10.1016/S0006-291X(03)00871-4. ISSN 0006-291X. PMID 12767928.
^ Strobel, T; Tai Y T, Korsmeyer S, Cannistra S A (Nov. 1998). "BAD partly reverses paclitaxel resistance in human ovarian cancer cells". Oncogene (ENGLAND) 17 (19): 2419–27. doi:10.1038/sj.onc.1202180. ISSN 0950-9232. PMID 9824152.
^ Zhang, Haichao; Nimmer Paul, Rosenberg Saul H, Ng Shi-Chung, Joseph Mary (Aug. 2002). "Development of a high-throughput fluorescence polarization assay for Bcl-x(L)". Anal. Biochem. (United States) 307 (1): 70–5. doi:10.1016/S0003-2697(02)00028-3. ISSN 0003-2697. PMID 12137781.
^ Gillissen, Bernhard; Essmann Frank, Graupner Vilma, Stärck Lilian, Radetzki Silke, Dörken Bernd, Schulze-Osthoff Klaus, Daniel Peter T (Jul. 2003). "Induction of cell death by the BH3-only Bcl-2 homolog Nbk/Bik is mediated by an entirely Bax-dependent mitochondrial pathway". EMBO J. (England) 22 (14): 3580–90. doi:10.1093/emboj/cdg343. ISSN 0261-4189. PMC 165613. PMID 12853473. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=165613.
^ Hoetelmans, R W M (Jun. 2004). "Nuclear partners of Bcl-2: Bax and PML". DNA Cell Biol. (United States) 23 (6): 351–4. doi:10.1089/104454904323145236. ISSN 1044-5498. PMID 15231068.
^ Lin, Bingzhen; Kolluri Siva Kumar, Lin Feng, Liu Wen, Han Young-Hoon, Cao Xihua, Dawson Marcia I, Reed John C, Zhang Xiao-kun (Feb. 2004). "Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3". Cell (United States) 116 (4): 527–40. doi:10.1016/S0092-8674(04)00162-X. ISSN 0092-8674. PMID 14980220.
^ Oltvai, Z N; Milliman C L, Korsmeyer S J (Aug. 1993). "Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death". Cell (UNITED STATES) 74 (4): 609–19. doi:10.1016/0092-8674(93)90509-O. ISSN 0092-8674. PMID 8358790.
^ Komatsu, K; Miyashita T, Hang H, Hopkins K M, Zheng W, Cuddeback S, Yamada M, Lieberman H B, Wang H G (Jan. 2000). "Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis". Nat. Cell Biol. (ENGLAND) 2 (1): 1–6. doi:10.1038/71316. ISSN 1465-7392. PMID 10620799.
^ Marzo, I; Brenner C, Zamzami N, Jürgensmeier J M, Susin S A, Vieira H L, Prévost M C, Xie Z, Matsuyama S, Reed J C, Kroemer G (Sep. 1998). "Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis". Science (UNITED STATES) 281 (5385): 2027–31. doi:10.1126/science.281.5385.2027. ISSN 0036-8075. PMID 9748162.
^ Zhang, H; Cowan-Jacob S W, Simonen M, Greenhalf W, Heim J, Meyhack B (Apr. 2000). "Structural basis of BFL-1 for its interaction with BAX and its anti-apoptotic action in mammalian and yeast cells". J. Biol. Chem. (UNITED STATES) 275 (15): 11092–9. doi:10.1074/jbc.275.15.11092. ISSN 0021-9258. PMID 10753914.
^ Nomura, Masaya; Shimizu Shigeomi, Sugiyama Tomoyasu, Narita Masashi, Ito Toshinori, Matsuda Hikaru, Tsujimoto Yoshihide (Jan. 2003). "14-3-3 Interacts directly with and negatively regulates pro-apoptotic Bax". J. Biol. Chem. (United States) 278 (3): 2058–65. doi:10.1074/jbc.M207880200. ISSN 0021-9258. PMID 12426317.

Lodish et al., Molecular Cell Biology (5th ed.) W.H. Freeman and Company, New York, 2003.
Miyashita, Toshiyuki; Reed, John C. (1995). "Tumor Suppressor p53 Is a Direct Transcriptional Activator of the Human bax Gene". Cell 80 (2): 293–299. doi:10.1016/0092-8674(95)90412-3. PMID 7834749.
Oltvai, Z.; Milliman, C.; Korsmeyer, S. J. (1993). "Bcl-2 Heterodimerizes in vivo with a Conserved Homolog, Bax, that Accelerates Programmed Cell Death". Cell 74 (4): 609–619. doi:10.1016/0092-8674(93)90509-O. PMID 8358790.

Bcl-2-associated X protein

Contents

Interactions

See also

References

Further reading