Bcl-2-associated death promoter

From Wikipedia, the free encyclopedia

BCL2-antagonist of cell death

Identifiers

BAD; BBC2; BCL2L8

External IDs

OMIM: 603167 MGI: 1096330 HomoloGene: 3189

Gene ontology
Molecular Function:	• protein binding
Cellular Component:	• cytoplasm • mitochondrion • mitochondrial outer membrane
Biological Process:	• glucose catabolic process • induction of apoptosis by extracellular signals • apoptotic program • glucose homeostasis • regulation of apoptosis • positive regulation of B cell differentiation • positive regulation of T cell differentiation

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_004322 (mRNA)
NP_004313 (protein)

NM_007522 (mRNA)
NP_031548 (protein)

Location

Chr 11: 63.79 - 63.81 Mb

Chr 19: 7.01 - 7.02 Mb

Pubmed search

[1]

[2]

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]

1 See also
2 References
3 Further reading
4 External links

[edit] See also

Programmed cell death

[edit] References

^ 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. doi:10.1210/me.11.12.1858.
^ Entrez Gene entry for BAD. NCBI. Retrieved on [[2006-12-19]].
^ 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. doi:10.1038/sj.cdd.4401097.
^ Helmreich, E.J.M. (2001) The Biochemistry of Cell Signalling, pp. 238-43
^ E.J.M. (2001) The Biochemistry of Cell Signalling, pp. 242
^ Foster, T.C. et al (2001) J. Neurosci. 21, 4066-4073, "Calcineurin Links Ca++ Dysregulation with Brain Aging"(

[edit] 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.