Bcl-2-associated death promoter

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BCL2-antagonist of cell death
Identifiers
Symbols BAD ; BBC2; BCL2L8
External IDs Template:OMIM5 Template:MGI HomoloGene: 3189
RNA expression pattern
More reference expression data
Orthologs
Template:GNF Ortholog box
Species Human Mouse
Entrez n/a n/a
Ensembl n/a n/a
UniProt n/a n/a
RefSeq (mRNA) n/a n/a
RefSeq (protein) n/a n/a
Location (UCSC) n/a n/a
PubMed search n/a n/a

The Bcl-2-associated death promoter (BAD) protein is a pro-apoptotic member of the Bcl-2 gene family which is involved in initiating apoptosis. It does not contain a C-terminal transmembrane domain for outer mitochondrial membrane and nuclear envelope targeting, unlike most other members of the Bcl-2 family [1]. Pro-apoptotic activation of this protein occurs through phosphorylation[2]. After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis.

BAD is a member of the BH3-only family [3], a subfamily of the Bcl-2 family.

The Bcl-2-associated death promoter (BAD) protein is a member of the Bcl-2 gene family. Some members of this family are pro-apoptotic (e.g., Bax, Bak) while others are anti-apoptotic (e.g., Bcl-2, Bcl-xL). Bax/Bak are believed to initiate apoptosis by forming a pore in the mitochondrial outer membrane that allows cytochrome c to escape into the cytoplasm and activate the pro-apoptotic caspase cascade. The anti-apoptotic Bcl proteins inhibit cytochrome c release through the mitochondrial pore and also inhibit activation of the cytoplasmic caspase cascade by cytochrome c.[4]

BAD does not contain a C-terminal transmembrane domain for outer mitochondrial membrane and nuclear envelope targeting, unlike most other members of the Bcl-2 family [1]. BAD is a member of the BH3-only family [3], a subfamily of the Bcl-2 family.

Dephosphorylated BAD forms a heterodimer with Bcl-2 and Bcl-xL, inactivating them and thus allowing Bax/Bak-triggered apoptosis. On the other hand, BAD phosphorylation by Akt/protein kinase B (triggered by PIP3), causes formation of the BAD-(14-3-3)protein heterodimer. This leaves Bcl-2 free to inhibit Bax-triggered apoptosis.[5] BAD phosphorylation is thus anti-apoptotic, and BAD dephosphorylation (e.g., by Ca++-stimulated Calcineurin) is pro-apoptotic. The latter may be involved in neural diseases such as schizophrenia.[6]

See also

References

  1. ↑ Sheau Yu Hsu; et al. (1997). "Interference of BAD (Bcl-xL/Bcl-2-Associated Death Promoter)-Induced Apoptosis in Mammalian Cells by 14–3-3 Isoforms and P11". Molecular Endocrinology. 11 (12): 1858-1867.
  2. ↑ "Entrez Gene entry for BAD". NCBI. Retrieved 2006-12-19. Check date values in: |accessdate= (help)
  3. ↑ Adachi M. and Imai K. (2002). "The proapoptotic BH3-only protein BAD transduces cell death signals independently of its interaction with Bcl-2". Cell death and differentiation. 9 (11): 1240-1247.
  4. ↑ Helmreich, E.J.M. (2001) The Biochemistry of Cell Signalling, pp. 238-43
  5. ↑ E.J.M. (2001) The Biochemistry of Cell Signalling, pp. 242
  6. ↑ Foster, T.C. et al (2001) J. Neurosci. 21, 4066-4073, "Calcineurin Links Ca++ Dysregulation with Brain Aging"(

Further reading

  • Tolstrup M, Ostergaard L, Laursen AL; et al. (2004). "HIV/SIV escape from immune surveillance: focus on Nef". Curr. HIV Res. 2 (2): 141–51. PMID 15078178.
  • Jiang P, Du W, Wu M (2007). "p53 and Bad: remote strangers become close friends". Cell Res. 17 (4): 283–5. doi:10.1038/cr.2007.19. PMID 17404594.
  • Yang E, Zha J, Jockel J; et al. (1995). "Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death". Cell. 80 (2): 285–91. PMID 7834748.
  • Zha J, Harada H, Yang E; et al. (1997). "Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L)". Cell. 87 (4): 619–28. PMID 8929531.
  • Wang HG, Rapp UR, Reed JC (1997). "Bcl-2 targets the protein kinase Raf-1 to mitochondria". Cell. 87 (4): 629–38. PMID 8929532.
  • Inohara N, Ding L, Chen S, Núñez G (1997). "harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L)". EMBO J. 16 (7): 1686–94. doi:10.1093/emboj/16.7.1686. PMID 9130713.
  • Zha J, Harada H, Osipov K; et al. (1997). "BH3 domain of BAD is required for heterodimerization with BCL-XL and pro-apoptotic activity". J. Biol. Chem. 272 (39): 24101–4. PMID 9305851.
  • Hsu SY, Kaipia A, Zhu L, Hsueh AJ (1997). "Interference of BAD (Bcl-xL/Bcl-2-associated death promoter)-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11". Mol. Endocrinol. 11 (12): 1858–67. PMID 9369453.
  • del Peso L, González-García M, Page C; et al. (1997). "Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt". Science. 278 (5338): 687–9. PMID 9381178.
  • Ottilie S, Diaz JL, Horne W; et al. (1998). "Dimerization properties of human BAD. Identification of a BH-3 domain and analysis of its binding to mutant BCL-2 and BCL-XL proteins". J. Biol. Chem. 272 (49): 30866–72. PMID 9388232.
  • Huang DC, Adams JM, Cory S (1998). "The conserved N-terminal BH4 domain of Bcl-2 homologues is essential for inhibition of apoptosis and interaction with CED-4". EMBO J. 17 (4): 1029–39. doi:10.1093/emboj/17.4.1029. PMID 9463381.
  • Blume-Jensen P, Janknecht R, Hunter T (1998). "The kit receptor promotes cell survival via activation of PI 3-kinase and subsequent Akt-mediated phosphorylation of Bad on Ser136". Curr. Biol. 8 (13): 779–82. PMID 9651683.
  • Strobel T, Tai YT, Korsmeyer S, Cannistra SA (1998). "BAD partly reverses paclitaxel resistance in human ovarian cancer cells". Oncogene. 17 (19): 2419–27. doi:10.1038/sj.onc.1202180. PMID 9824152.
  • Song Q, Kuang Y, Dixit VM, Vincenz C (1999). "Boo, a novel negative regulator of cell death, interacts with Apaf-1". EMBO J. 18 (1): 167–78. doi:10.1093/emboj/18.1.167. PMID 9878060.
  • Yasuda M, Han JW, Dionne CA; et al. (1999). "BNIP3alpha: a human homolog of mitochondrial proapoptotic protein BNIP3". Cancer Res. 59 (3): 533–7. PMID 9973195.
  • Wang HG, Pathan N, Ethell IM; et al. (1999). "Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD". Science. 284 (5412): 339–43. PMID 10195903.
  • Holmgreen SP, Huang DC, Adams JM, Cory S (1999). "Survival activity of Bcl-2 homologs Bcl-w and A1 only partially correlates with their ability to bind pro-apoptotic family members". Cell Death Differ. 6 (6): 525–32. doi:10.1038/sj.cdd.4400519. PMID 10381646.
  • Ostrerova N, Petrucelli L, Farrer M; et al. (1999). "alpha-Synuclein shares physical and functional homology with 14-3-3 proteins". J. Neurosci. 19 (14): 5782–91. PMID 10407019.
  • Scheid MP, Schubert KM, Duronio V (1999). "Regulation of bad phosphorylation and association with Bcl-x(L) by the MAPK/Erk kinase". J. Biol. Chem. 274 (43): 31108–13. PMID 10521512.
  • Bonni A, Brunet A, West AE; et al. (1999). "Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms". Science. 286 (5443): 1358–62. PMID 10558990.


External links

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