View source for Biology:Bcl-2-associated death promoter

{{Infobox_gene}}
{{Infobox protein family
| Symbol = Bcl-2_BAD
| Name = Pro-apoptotic Bcl-2 protein, BAD
| image = PDB 1g5j EBI.jpg
| width =
| caption = complex of bcl-xl with peptide from bad
| Pfam = PF10514
| Pfam_clan =
| InterPro = IPR018868
| SMART =
| PROSITE =
| MEROPS =
| SCOP =
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
}}
The '''BCL2 associated agonist of cell death<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/572#gene-expression|title = BAD BCL2 associated agonist of cell death &#91;Homo sapiens (Human)&#93; - Gene - NCBI}}</ref>''' ('''BAD''') [[Biology:Protein|protein]] is a [[Biology:Apoptosis|pro-apoptotic]] member of the [[Biology:Bcl-2|Bcl-2]] gene family which is involved in initiating [[Biology:Apoptosis|apoptosis]]. BAD is a member of the BH3-only family,<ref name="adachi">{{cite journal | vauthors = Adachi M, Imai K | title = The proapoptotic BH3-only protein BAD transduces cell death signals independently of its interaction with Bcl-2 | journal = Cell Death Differ. | volume = 9 | issue = 11 | pages = 1240–7 | year = 2002 | pmid = 12404123 | doi = 10.1038/sj.cdd.4401097 | doi-access = free }}</ref> a subfamily of the [[Biology:Bcl-2|Bcl-2 family]]. It does not contain a C-terminal transmembrane [[Biology:Protein domain|domain]] for outer mitochondrial membrane and [[Biology:Nuclear envelope|nuclear envelope]] targeting, unlike most other members of the [[Biology:Bcl-2|Bcl-2 family]].<ref name="sheau">{{cite journal | vauthors = 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 | doi = 10.1210/mend.11.12.0023 | pmid = 9369453 | doi-access = free }}</ref> After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis.

== Mechanism of action ==
[[Biology:Bcl-2-associated X protein|Bax]]/[[Biology:Bcl-2 homologous antagonist killer|Bak]] are believed to initiate apoptosis by forming a pore in the mitochondrial outer membrane that allows [[Biology:Cytochrome c|cytochrome c]] to escape into the cytoplasm and activate the pro-apoptotic caspase cascade.  The anti-apoptotic [[Biology:Bcl-2|Bcl-2]] and [[Biology:Bcl-xL|Bcl-xL]] proteins inhibit cytochrome c release through the mitochondrial pore and also inhibit activation of the cytoplasmic caspase cascade by cytochrome c.<ref>Helmreich, E.J.M. (2001) The Biochemistry of Cell Signalling, pp. 238-43</ref>

Dephosphorylated BAD forms a heterodimer with [[Biology:Bcl-2|Bcl-2]] and [[Biology:Bcl-xL|Bcl-xL]], inactivating them and thus allowing [[Biology:Bcl-2-associated X protein|Bax]]/[[Biology:Bcl-2 homologous antagonist killer|Bak]]-triggered apoptosis.  When BAD is phosphorylated by Akt/protein kinase B (triggered by PIP<sub>3</sub>), it forms the BAD-(14-3-3) protein heterodimer.  This leaves [[Biology:Bcl-2|Bcl-2]] free to inhibit [[Biology:Bcl-2-associated X protein|Bax]]-triggered apoptosis.<ref>E.J.M. (2001) The Biochemistry of Cell Signalling, pp. 242</ref>  BAD phosphorylation is thus anti-apoptotic, and BAD dephosphorylation (e.g., by Ca<sup>2+</sup>-stimulated [[Biology:Calcineurin|Calcineurin]]) is pro-apoptotic.  The latter may be involved in neural diseases such as schizophrenia.<ref>Foster, T.C. et al. (2001) J. Neurosci. 21, 4066-4073, "Calcineurin Links Ca++ Dysregulation with Brain Aging"(</ref>

== Interactions ==
[[Image:Signal transduction pathways.svg|300px|thumb|left|Overview of signal transduction pathways involved with apoptosis.]]
Bcl-2-associated death promoter has been shown to interact with:
{{div col|colwidth=20em}}
* BCL2L1<ref name = pmid15694340>{{cite journal | vauthors = Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC | title = Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function | journal = Mol. Cell | volume = 17 | issue = 3 | pages = 393–403  | date = February 2005 | pmid = 15694340 | doi = 10.1016/j.molcel.2004.12.030 | doi-access = free }}</ref><ref name = pmid15705582>{{cite journal | vauthors = Jin Z, Xin M, Deng X | title = Survival function of protein kinase C{iota} as a novel nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-activated bad kinase | journal = J. Biol. Chem. | volume = 280 | issue = 16 | pages = 16045–52 | date = April 2005 | pmid = 15705582 | doi = 10.1074/jbc.M413488200 | doi-access = free }}</ref><ref name = pmid9824152>{{cite journal | vauthors = 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  | date = November 1998 | pmid = 9824152 | doi = 10.1038/sj.onc.1202180 | doi-access = free }}</ref><ref name = pmid12137781>{{cite journal | vauthors = Zhang H, Nimmer P, Rosenberg SH, Ng SC, Joseph M | title = Development of a high-throughput fluorescence polarization assay for Bcl-x(L) | journal = Anal. Biochem. | volume = 307 | issue = 1 | pages = 70–5  | date = August 2002 | pmid = 12137781 | doi = 10.1016/S0003-2697(02)00028-3 }}</ref><ref name = pmid12115603>{{cite journal | vauthors = Ayllón V, Cayla X, García A, Fleischer A, Rebollo A | title = The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad | journal = Eur. J. Immunol. | volume = 32 | issue = 7 | pages = 1847–55  | date = July 2002 | pmid = 12115603 | doi = 10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7 | doi-access = free }}</ref><ref name = pmid10620799>{{cite journal | vauthors = Komatsu K, Miyashita T, Hang H, Hopkins KM, Zheng W, Cuddeback S, Yamada M, Lieberman HB, Wang HG | title = Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis | journal = Nat. Cell Biol. | volume = 2 | issue = 1 | pages = 1–6  | date = January 2000 | pmid = 10620799 | doi = 10.1038/71316 | s2cid = 52847351 }}</ref><ref name = pmid7834748>{{cite journal | vauthors = Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ | 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  | date = January 1995 | pmid = 7834748 | doi = 10.1016/0092-8674(95)90411-5 | s2cid = 10343291 | doi-access = free }}</ref><ref name = pmid11206074>{{cite journal | vauthors = Petros AM, Nettesheim DG, Wang Y, Olejniczak ET, Meadows RP, Mack J, Swift K, Matayoshi ED, Zhang H, Thompson CB, Fesik SW | title = Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies | journal = Protein Sci. | volume = 9 | issue = 12 | pages = 2528–34  | date = Dec 2000 | pmid = 11206074 | pmc = 2144516 | doi = 10.1110/ps.9.12.2528 }}</ref><ref name = pmid11494146>{{cite journal | vauthors = Chattopadhyay A, Chiang CW, Yang E | title = BAD/BCL-[X(L)] heterodimerization leads to bypass of G0/G1 arrest | journal = Oncogene | volume = 20 | issue = 33 | pages = 4507–18  | date = July 2001 | pmid = 11494146 | doi = 10.1038/sj.onc.1204584 | doi-access = free }}</ref><ref name = pmid9389483>{{cite journal | vauthors = Iwahashi H, Eguchi Y, Yasuhara N, Hanafusa T, Matsuzawa Y, Tsujimoto Y | title = Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy | journal = Nature | volume = 390 | issue = 6658 | pages = 413–7  | date = November 1997 | pmid = 9389483 | doi = 10.1038/37144 | bibcode = 1997Natur.390..413I | s2cid = 1936633 }}</ref><ref name = pmid11077446>{{cite journal | vauthors = Komatsu K, Wharton W, Hang H, Wu C, Singh S, Lieberman HB, Pledger WJ, Wang HG | title = PCNA interacts with hHus1/hRad9 in response to DNA damage and replication inhibition | journal = Oncogene | volume = 19 | issue = 46 | pages = 5291–7  | date = November 2000 | pmid = 11077446 | doi = 10.1038/sj.onc.1203901 | doi-access = free }}</ref> 
* BCL2A1<ref name = pmid15694340/><ref name = pmid11483855/> 
* [[Biology:BCL2L2|BCL2L2]]<ref name = pmid15694340/><ref name = pmid12115603/><ref name = pmid11483855>{{cite journal | vauthors = Bae J, Hsu SY, Leo CP, Zell K, Hsueh AJ | title = Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis | journal = Apoptosis | volume = 6 | issue = 5 | pages = 319–30  | date = October 2001 | pmid = 11483855 | doi = 10.1023/A:1011319901057 | s2cid = 23119757 }}</ref><ref name = pmid10381646>{{cite journal | vauthors = 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  | date = June 1999 | pmid = 10381646 | doi = 10.1038/sj.cdd.4400519 | doi-access = free }}</ref> 
* [[Biology:Bcl-2|Bcl-2]]<ref name = pmid15694340/><ref name = pmid7834748/> 
* MCL1<ref name = pmid15694340/><ref name = pmid11483855/> 
* [[Biology:S100A10|S100A10]]<ref name = pmid9369453/>
* [[Biology:YWHAQ|YWHAQ]]<ref name = pmid15694340/><ref name = pmid9369453>{{cite journal | vauthors = 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  | date = November 1997 | doi = 10.1210/mend.11.12.0023 | pmid = 9369453 | doi-access = free }}</ref>  and
* [[Biology:YWHAZ|YWHAZ]]<ref name = pmid11410287>{{cite journal | vauthors = Yang H, Masters SC, Wang H, Fu H | title = The proapoptotic protein Bad binds the amphipathic groove of 14-3-3zeta | journal = Biochim. Biophys. Acta | volume = 1547 | issue = 2 | pages = 313–9  | date = June 2001 | pmid = 11410287 | doi = 10.1016/S0167-4838(01)00202-3 }}</ref> 
{{Div col end}}

== See also ==
*[[Biology:Programmed cell death|Programmed cell death]]
{{Clear}}

== References ==
{{Reflist|35em}}

== Further reading ==
{{Refbegin|35em}}
* {{cite journal | vauthors = Tolstrup M, Ostergaard L, Laursen AL, Pedersen SF, Duch M | 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 = 10.2174/1570162043484924 }}
* {{cite journal | vauthors = 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 | doi-access = free }}
* {{cite journal | vauthors = Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ | 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 = 10.1016/0092-8674(95)90411-5 | s2cid = 10343291 | doi-access = free }}
* {{cite journal | vauthors = Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ | 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 = 1996 | pmid = 8929531 | doi = 10.1016/S0092-8674(00)81382-3 | s2cid = 860908 | doi-access = free }}
* {{cite journal | vauthors = 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 = 1996 | pmid = 8929532 | doi = 10.1016/S0092-8674(00)81383-5 | s2cid = 16559750 | doi-access = free }}
* {{cite journal | vauthors = 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 | pmc = 1169772 | doi = 10.1093/emboj/16.7.1686 }}
* {{cite journal | vauthors = Zha J, Harada H, Osipov K, Jockel J, Waksman G, Korsmeyer SJ | 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 = 10.1074/jbc.272.39.24101 | doi-access = free }}
* {{cite journal | vauthors = 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 | doi = 10.1210/mend.11.12.0023 | pmid = 9369453 | doi-access = free }}
* {{cite journal | vauthors = del Peso L, González-García M, Page C, Herrera R, Nuñez G | 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 = 10.1126/science.278.5338.687 | bibcode = 1997Sci...278..687D }}
* {{cite journal | vauthors = Ottilie S, Diaz JL, Horne W, Chang J, Wang Y, Wilson G, Chang S, Weeks S, Fritz LC, Oltersdorf T | 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 = 1997 | pmid = 9388232 | doi = 10.1074/jbc.272.49.30866 | doi-access = free }}
* {{cite journal | vauthors = 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 | pmc = 1170452 | doi = 10.1093/emboj/17.4.1029 }}
* {{cite journal | vauthors = 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 = 10.1016/S0960-9822(98)70302-1 | s2cid = 15596347 | doi-access = free }}
* {{cite journal | vauthors = 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 | doi-access = free }}
* {{cite journal | vauthors = 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 | pmc = 1171112 | doi = 10.1093/emboj/18.1.167 }}
* {{cite journal | vauthors = Yasuda M, Han JW, Dionne CA, Boyd JM, Chinnadurai G | title = BNIP3alpha: a human homolog of mitochondrial proapoptotic protein BNIP3 | journal = Cancer Res. | volume = 59 | issue = 3 | pages = 533–7 | year = 1999 | pmid = 9973195 }}
* {{cite journal | vauthors = Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF, Reed JC | title = Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD | journal = Science | volume = 284 | issue = 5412 | pages = 339–43 | year = 1999 | pmid = 10195903 | doi = 10.1126/science.284.5412.339 | bibcode = 1999Sci...284..339W }}
* {{cite journal | vauthors = 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 | doi-access = free }}
* {{cite journal | vauthors = Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J, Wolozin B | author7-link=Benjamin Wolozin | 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 =  10.1523/JNEUROSCI.19-14-05782.1999| pmc=6783081 | doi-access = free }}
* {{cite journal | vauthors = 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 = 10.1074/jbc.274.43.31108 | doi-access = free }}
* {{cite journal | vauthors = Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME | 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 = 10.1126/science.286.5443.1358 }}
{{Refend}}

== External links ==
* {{MeshName|bcl-Associated+Death+Protein}}
* {{UCSC gene info|BAD}}

{{Fas apoptosis signaling pathway}}

{{DEFAULTSORT:Bcl-2-Associated Death Promoter}}
[[Category:Programmed cell death]]
[[Category:Proteins]]

{{Sourceattribution|Bcl-2-associated death promoter}}