Bcl-2-associated death promoter
BCL2-antagonist of cell death
|RNA expression pattern|
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.
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 . BAD is a member of the BH3-only family , 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.
- ↑ 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).
- ↑ 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).
- ↑ 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"(
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