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. BAD is a member of the BH3-only family ,[1] a subfamily of the Bcl-2 family. 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.[2] After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis.
Mechanism of Action
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-2 and Bcl-xL proteins inhibit cytochrome c release through the mitochondrial pore and also inhibit activation of the cytoplasmic caspase cascade by cytochrome c.[3]
Dephosphorylated BAD forms a heterodimer with Bcl-2 and Bcl-xL, inactivating them and thus allowing Bax/Bak-triggered apoptosis. When BAD is phosphorylated by Akt/protein kinase B (triggered by PIP3), it forms the BAD-(14-3-3)protein homodimer. This leaves Bcl-2 free to inhibit Bax-triggered apoptosis.[4] BAD phosphorylation is thus anti-apoptotic, and BAD dephosphorylation (e.g., by Ca2+-stimulated Calcineurin) is pro-apoptotic. The latter may be involved in neural diseases such as schizophrenia.[5]
Interactions
Bcl-2-associated death promoter has been shown to interact with BCL2-like 1,[6][7][8][9][10][11][12][13][14][15][16] BCL2L2,[6][10][17][18] Bcl-2,[6][12] BCL2-related protein A1,[6][17] YWHAQ,[6][19] YWHAZ,[20] MCL1[6][17] and S100A10.[19]
See also
References
- ^ 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. PMID 12404123. http://www.nature.com/cdd/journal/v9/n11/abs/4401097a.html.
- ^ 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. PMID 9369453. http://mend.endojournals.org/cgi/content/full/11/12/1858.
- ^ 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"(
- ^ a b c d e f Chen, Lin; Willis Simon N, Wei Andrew, Smith Brian J, Fletcher Jamie I, Hinds Mark G, Colman Peter M, Day Catherine L, Adams Jerry M, Huang David C S (Feb. 2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function". Mol. Cell (United States) 17 (3): 393–403. doi:10.1016/j.molcel.2004.12.030. ISSN 1097-2765. PMID 15694340.
- ^ Jin, Zhaohui; Xin Meiguo, Deng Xingming (Apr. 2005). "Survival function of protein kinase C{iota} as a novel nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-activated bad kinase". J. Biol. Chem. (United States) 280 (16): 16045–52. doi:10.1074/jbc.M413488200. ISSN 0021-9258. PMID 15705582.
- ^ Strobel, T; Tai Y T, Korsmeyer S, Cannistra S A (Nov. 1998). "BAD partly reverses paclitaxel resistance in human ovarian cancer cells". Oncogene (ENGLAND) 17 (19): 2419–27. doi:10.1038/sj.onc.1202180. ISSN 0950-9232. PMID 9824152.
- ^ Zhang, Haichao; Nimmer Paul, Rosenberg Saul H, Ng Shi-Chung, Joseph Mary (Aug. 2002). "Development of a high-throughput fluorescence polarization assay for Bcl-x(L)". Anal. Biochem. (United States) 307 (1): 70–5. doi:10.1016/S0003-2697(02)00028-3. ISSN 0003-2697. PMID 12137781.
- ^ a b Ayllón, Verónica; Cayla Xavier, García Alphonse, Fleischer Aarne, Rebollo Angelita (Jul. 2002). "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad". Eur. J. Immunol. (Germany) 32 (7): 1847–55. doi:10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7. ISSN 0014-2980. PMID 12115603.
- ^ Komatsu, K; Miyashita T, Hang H, Hopkins K M, Zheng W, Cuddeback S, Yamada M, Lieberman H B, Wang H G (Jan. 2000). "Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis". Nat. Cell Biol. (ENGLAND) 2 (1): 1–6. doi:10.1038/71316. ISSN 1465-7392. PMID 10620799.
- ^ a b Yang, E; Zha J, Jockel J, Boise L H, Thompson C B, Korsmeyer S J (Jan. 1995). "Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death". Cell (UNITED STATES) 80 (2): 285–91. doi:10.1016/0092-8674(95)90411-5. ISSN 0092-8674. PMID 7834748.
- ^ Petros, A M; Nettesheim D G, Wang Y, Olejniczak E T, Meadows R P, Mack J, Swift K, Matayoshi E D, Zhang H, Thompson C B, Fesik S W (Dec. 2000). "Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies". Protein Sci. (United States) 9 (12): 2528–34. doi:10.1110/ps.9.12.2528. ISSN 0961-8368. PMC 2144516. PMID 11206074. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2144516.
- ^ Chattopadhyay, A; Chiang C W, Yang E (Jul. 2001). "BAD/BCL-[X(L)] heterodimerization leads to bypass of G0/G1 arrest". Oncogene (England) 20 (33): 4507–18. doi:10.1038/sj.onc.1204584. ISSN 0950-9232. PMID 11494146.
- ^ Iwahashi, H; Eguchi Y, Yasuhara N, Hanafusa T, Matsuzawa Y, Tsujimoto Y (Nov. 1997). "Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy". Nature (ENGLAND) 390 (6658): 413–7. doi:10.1038/37144. ISSN 0028-0836. PMID 9389483.
- ^ Komatsu, K; Wharton W, Hang H, Wu C, Singh S, Lieberman H B, Pledger W J, Wang H G (Nov. 2000). "PCNA interacts with hHus1/hRad9 in response to DNA damage and replication inhibition". Oncogene (ENGLAND) 19 (46): 5291–7. doi:10.1038/sj.onc.1203901. ISSN 0950-9232. PMID 11077446.
- ^ a b c Bae, J; Hsu S Y, Leo C P, Zell K, Hsueh A J (Oct. 2001). "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis". Apoptosis (United States) 6 (5): 319–30. doi:10.1023/A:1011319901057. ISSN 1360-8185. PMID 11483855.
- ^ Holmgreen, S P; Huang D C, Adams J M, Cory S (Jun. 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. (ENGLAND) 6 (6): 525–32. doi:10.1038/sj.cdd.4400519. ISSN 1350-9047. PMID 10381646.
- ^ a b Hsu, S Y; Kaipia A, Zhu L, Hsueh A J (Nov. 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. (UNITED STATES) 11 (12): 1858–67. doi:10.1210/me.11.12.1858. ISSN 0888-8809. PMID 9369453.
- ^ Yang, H; Masters S C, Wang H, Fu H (Jun. 2001). "The proapoptotic protein Bad binds the amphipathic groove of 14-3-3zeta". Biochim. Biophys. Acta (Netherlands) 1547 (2): 313–9. ISSN 0006-3002. PMID 11410287.
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. doi:10.2174/1570162043484924. 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. doi:10.1016/0092-8674(95)90411-5. 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. doi:10.1016/S0092-8674(00)81382-3. PMID 8929531.
- Wang HG, Rapp UR, Reed JC (1997). "Bcl-2 targets the protein kinase Raf-1 to mitochondria". Cell 87 (4): 629–38. doi:10.1016/S0092-8674(00)81383-5. 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. PMC 1169772. PMID 9130713. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1169772.
- 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. doi:10.1074/jbc.272.39.24101. 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. doi:10.1210/me.11.12.1858. 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. doi:10.1126/science.278.5338.687. 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. doi:10.1074/jbc.272.49.30866. 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. PMC 1170452. PMID 9463381. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170452.
- 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. doi:10.1016/S0960-9822(98)70302-1. 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. PMC 1171112. PMID 9878060. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171112.
- 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. doi:10.1126/science.284.5412.339. 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. doi:10.1074/jbc.274.43.31108. 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. doi:10.1126/science.286.5443.1358. PMID 10558990.
External links
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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