Bcl-2-associated death promoter

BCL2-antagonist of cell death
Identifiers
Symbol(s)	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
Entrez	572	12015
Ensembl	ENSG00000002330	ENSMUSG00000024959
Uniprot	Q92934	Q3TFU7
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 . Pro-apoptotic activation of this protein occurs through phosphorylation. 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 , 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.

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. 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.

See also

• Programmed cell death

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

• MeSH bcl-Associated+Death+ProteinTemplate:Molecular-biology-stub