Bcl-2-associated death promoter

Mammalian protein found in Homo sapiens
BAD
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1G5J

Identifiers
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]
Gene location (Mouse)
Chromosome 19 (mouse)
Chr.Chromosome 19 (mouse)[2]
Chromosome 19 (mouse)
Genomic location for BAD
Genomic location for BAD
Band19|19 AStart6,919,229 bp[2]
End6,929,267 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • body of stomach

  • right coronary artery

  • left coronary artery

  • left lobe of thyroid gland

  • right uterine tube

  • ascending aorta

  • right adrenal gland

  • right lobe of thyroid gland

  • left uterine tube

  • popliteal artery
Top expressed in
  • blastocyst

  • internal carotid artery

  • external carotid artery

  • lip

  • facial motor nucleus

  • duodenum

  • pyloric antrum

  • morula

  • proximal tubule

  • aortic valve
More reference expression data
BioGPS


More reference expression data
Gene ontology
Molecular function
  • 14-3-3 protein binding
  • protein phosphatase binding
  • protein binding
  • protein heterodimerization activity
  • cysteine-type endopeptidase activator activity involved in apoptotic process
  • phospholipid binding
  • protein kinase binding
  • lipid binding
  • protein phosphatase 2B binding
  • protein kinase B binding
Cellular component
  • cytoplasm
  • cytosol
  • membrane
  • mitochondrial outer membrane
  • mitochondrion
Biological process
  • positive regulation of T cell differentiation
  • cellular response to hypoxia
  • regulation of apoptotic process
  • response to amino acid
  • response to estradiol
  • response to hypoxia
  • positive regulation of type B pancreatic cell development
  • response to organic cyclic compound
  • extrinsic apoptotic signaling pathway
  • positive regulation of autophagy
  • glucose homeostasis
  • cytokine-mediated signaling pathway
  • response to testosterone
  • positive regulation of epithelial cell proliferation
  • positive regulation of B cell differentiation
  • response to progesterone
  • positive regulation of apoptotic process by virus
  • pore complex assembly
  • cellular response to nicotine
  • response to glucocorticoid
  • positive regulation of neuron death
  • response to glucose
  • regulation of cysteine-type endopeptidase activity involved in apoptotic process
  • response to organic substance
  • response to calcium ion
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
  • ATP metabolic process
  • cellular response to mechanical stimulus
  • activation of cysteine-type endopeptidase activity
  • regulation of mitochondrial membrane permeability
  • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
  • positive regulation of intrinsic apoptotic signaling pathway
  • positive regulation of glucokinase activity
  • spermatogenesis
  • glucose catabolic process
  • intrinsic apoptotic signaling pathway in response to DNA damage
  • positive regulation of proteolysis
  • cerebral cortex development
  • extrinsic apoptotic signaling pathway in absence of ligand
  • cellular response to lipid
  • positive regulation of release of cytochrome c from mitochondria
  • response to hormone
  • positive regulation of mitochondrial membrane potential
  • positive regulation of insulin secretion involved in cellular response to glucose stimulus
  • suppression by virus of host apoptotic process
  • response to ethanol
  • ADP metabolic process
  • activation of cysteine-type endopeptidase activity involved in apoptotic process
  • cell population proliferation
  • type B pancreatic cell proliferation
  • cellular response to chromate
  • extrinsic apoptotic signaling pathway via death domain receptors
  • response to hydrogen peroxide
  • response to oleic acid
  • release of cytochrome c from mitochondria
  • positive regulation of insulin secretion
  • apoptotic process
  • intrinsic apoptotic signaling pathway
  • apoptotic signaling pathway
  • protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
  • positive regulation of intrinsic apoptotic signaling pathway in response to osmotic stress
  • positive regulation of apoptotic process
  • positive regulation of granulosa cell apoptotic process
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

572

12015

Ensembl

ENSG00000002330

ENSMUSG00000024959

UniProt

Q92934

Q61337

RefSeq (mRNA)

NM_032989
NM_004322

NM_007522
NM_001285453

RefSeq (protein)

NP_004313
NP_116784

NP_001272382
NP_031548

Location (UCSC)Chr 11: 64.27 – 64.28 MbChr 19: 6.92 – 6.93 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Pro-apoptotic Bcl-2 protein, BAD
complex of bcl-xl with peptide from bad
Identifiers
SymbolBcl-2_BAD
PfamPF10514
InterProIPR018868
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

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.

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.[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]

Interactions

Overview of signal transduction pathways involved with apoptosis.

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

See also

References

  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. ^ "BAD BCL2 associated agonist of cell death [Homo sapiens (Human)] - Gene - NCBI".
  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/mend.11.12.0023. 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. S2CID 52847351.
  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. S2CID 10343291.
  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. Bibcode:1997Natur.390..413I. doi:10.1038/37144. PMID 9389483. S2CID 1936633.
  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. S2CID 23119757.
  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/mend.11.12.0023. 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 reading

  • Tolstrup M, Ostergaard L, Laursen AL, Pedersen SF, Duch M (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, Boise LH, Thompson CB, Korsmeyer SJ (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. S2CID 10343291.
  • Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ (1996). "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. S2CID 860908.
  • Wang HG, Rapp UR, Reed JC (1996). "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. S2CID 16559750.
  • 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.
  • Zha J, Harada H, Osipov K, Jockel J, Waksman G, Korsmeyer SJ (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/mend.11.12.0023. PMID 9369453.
  • del Peso L, González-García M, Page C, Herrera R, Nuñez G (1997). "Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt". Science. 278 (5338): 687–9. Bibcode:1997Sci...278..687D. doi:10.1126/science.278.5338.687. PMID 9381178.
  • Ottilie S, Diaz JL, Horne W, Chang J, Wang Y, Wilson G, Chang S, Weeks S, Fritz LC, Oltersdorf T (1997). "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.
  • 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. Bibcode:1998CBio....8..779B. doi:10.1016/S0960-9822(98)70302-1. PMID 9651683. S2CID 15596347.
  • 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.
  • Yasuda M, Han JW, Dionne CA, Boyd JM, Chinnadurai G (1999). "BNIP3alpha: a human homolog of mitochondrial proapoptotic protein BNIP3". Cancer Res. 59 (3): 533–7. PMID 9973195.
  • Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF, Reed JC (1999). "Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD". Science. 284 (5412): 339–43. Bibcode:1999Sci...284..339W. 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, Mehta N, Choi P, Hardy J, Wolozin B (1999). "alpha-Synuclein shares physical and functional homology with 14-3-3 proteins". J. Neurosci. 19 (14): 5782–91. doi:10.1523/JNEUROSCI.19-14-05782.1999. PMC 6783081. 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, Datta SR, Takasu MA, Greenberg ME (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