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The BCL2 associated agonist of cell death[5] (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,[6] 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.[7] After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis.

Available structures
PDBOrtholog search: PDBe RCSB
AliasesBAD, BBC2, BCL2L8, BCL2 associated agonist of cell death
External IDsOMIM: 603167 MGI: 1096330 HomoloGene: 3189 GeneCards: BAD
Gene location (Human)
Chromosome 11 (human)
Chr.Chromosome 11 (human)[1]
Chromosome 11 (human)
Genomic location for BAD
Genomic location for BAD
Band11q13.1Start64,269,830 bp[1]
End64,284,704 bp[1]
RNA expression pattern
PBB GE BAD 1861 at fs.png

PBB GE BAD 209364 at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 11: 64.27 – 64.28 MbChr 19: 6.94 – 6.95 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse
Pro-apoptotic Bcl-2 protein, BAD
PDB 1g5j EBI.jpg
complex of bcl-xl with peptide from bad

Mechanism of actionEdit

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.[8]

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 heterodimer. This leaves Bcl-2 free to inhibit Bax-triggered apoptosis.[9] 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.[10]


Overview of signal transduction pathways involved with apoptosis.

Bcl-2-associated death promoter has been shown to interact with:

See alsoEdit


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000002330 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024959 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^
  6. ^ Adachi M, Imai K (2002). "The proapoptotic BH3-only protein BAD transduces cell death signals independently of its interaction with Bcl-2". Cell Death Differ. 9 (11): 1240–7. doi:10.1038/sj.cdd.4401097. PMID 12404123.
  7. ^ 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.
  8. ^ Helmreich, E.J.M. (2001) The Biochemistry of Cell Signalling, pp. 238-43
  9. ^ E.J.M. (2001) The Biochemistry of Cell Signalling, pp. 242
  10. ^ Foster, T.C. et al. (2001) J. Neurosci. 21, 4066-4073, "Calcineurin Links Ca++ Dysregulation with Brain Aging"(
  11. ^ a b c d e f Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC (February 2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function". Mol. Cell. 17 (3): 393–403. doi:10.1016/j.molcel.2004.12.030. PMID 15694340.
  12. ^ Jin Z, Xin M, Deng X (April 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. 280 (16): 16045–52. doi:10.1074/jbc.M413488200. PMID 15705582.
  13. ^ Strobel T, Tai YT, Korsmeyer S, Cannistra SA (November 1998). "BAD partly reverses paclitaxel resistance in human ovarian cancer cells". Oncogene. 17 (19): 2419–27. doi:10.1038/sj.onc.1202180. PMID 9824152.
  14. ^ Zhang H, Nimmer P, Rosenberg SH, Ng SC, Joseph M (August 2002). "Development of a high-throughput fluorescence polarization assay for Bcl-x(L)". Anal. Biochem. 307 (1): 70–5. doi:10.1016/S0003-2697(02)00028-3. PMID 12137781.
  15. ^ a b Ayllón V, Cayla X, García A, Fleischer A, Rebollo A (July 2002). "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad". Eur. J. Immunol. 32 (7): 1847–55. doi:10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7. PMID 12115603.
  16. ^ Komatsu K, Miyashita T, Hang H, Hopkins KM, Zheng W, Cuddeback S, Yamada M, Lieberman HB, Wang HG (January 2000). "Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis". Nat. Cell Biol. 2 (1): 1–6. doi:10.1038/71316. PMID 10620799.
  17. ^ a b Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ (January 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.
  18. ^ Petros AM, Nettesheim DG, Wang Y, Olejniczak ET, Meadows RP, Mack J, Swift K, Matayoshi ED, Zhang H, Thompson CB, Fesik SW (Dec 2000). "Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies". Protein Sci. 9 (12): 2528–34. doi:10.1110/ps.9.12.2528. PMC 2144516. PMID 11206074.
  19. ^ Chattopadhyay A, Chiang CW, Yang E (July 2001). "BAD/BCL-[X(L)] heterodimerization leads to bypass of G0/G1 arrest". Oncogene. 20 (33): 4507–18. doi:10.1038/sj.onc.1204584. PMID 11494146.
  20. ^ Iwahashi H, Eguchi Y, Yasuhara N, Hanafusa T, Matsuzawa Y, Tsujimoto Y (November 1997). "Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy". Nature. 390 (6658): 413–7. doi:10.1038/37144. PMID 9389483.
  21. ^ Komatsu K, Wharton W, Hang H, Wu C, Singh S, Lieberman HB, Pledger WJ, Wang HG (November 2000). "PCNA interacts with hHus1/hRad9 in response to DNA damage and replication inhibition". Oncogene. 19 (46): 5291–7. doi:10.1038/sj.onc.1203901. PMID 11077446.
  22. ^ a b c Bae J, Hsu SY, Leo CP, Zell K, Hsueh AJ (October 2001). "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis". Apoptosis. 6 (5): 319–30. doi:10.1023/A:1011319901057. PMID 11483855.
  23. ^ Holmgreen SP, Huang DC, Adams JM, Cory S (June 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.
  24. ^ a b Hsu SY, Kaipia A, Zhu L, Hsueh AJ (November 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.
  25. ^ Yang H, Masters SC, Wang H, Fu H (June 2001). "The proapoptotic protein Bad binds the amphipathic groove of 14-3-3zeta". Biochim. Biophys. Acta. 1547 (2): 313–9. doi:10.1016/S0167-4838(01)00202-3. PMID 11410287.

Further readingEdit

External linksEdit