Bcl-2-associated death promoter


Bcl-2-associated death promoter

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 familycite journal | author=Sheau Yu Hsu, "et al."| title=Interference of BAD (Bcl-xL/Bcl-2-Associated Death Promoter)-Induced Apoptosis in Mammalian Cells by 14–3-3 Isoforms and P11| journal=Molecular Endocrinology| year=1997| volume=11| issue=12| url=http://mend.endojournals.org/cgi/content/full/11/12/1858| pages=1858–1867| doi=10.1210/me.11.12.1858] .Pro-apoptotic activation of this protein occurs through phosphorylationCite web|url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=572|title=Entrez Gene entry for BAD|accessdate=2006-12-19|publisher=NCBI] . 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 familycite journal | author=Adachi M. and Imai K. | title=The proapoptotic BH3-only protein BAD transduces cell death signals independently of its interaction with Bcl-2|journal=Cell death and differentiation |year=2002 |volume=9 |issue=11| url=http://www.nature.com/cdd/journal/v9/n11/abs/4401097a.html |pages=1240–1247 | doi=10.1038/sj.cdd.4401097] , 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. [Helmreich, E.J.M. (2001) The Biochemistry of Cell Signalling, pp. 238-43]

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. [E.J.M. (2001) The Biochemistry of Cell Signalling, pp. 242] 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. [Foster, T.C. et al (2001) J. Neurosci. 21, 4066-4073, "Calcineurin Links Ca++ Dysregulation with Brain Aging"(]

See also

*Programmed cell death

References

Further reading

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

External links

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