Bcl-2-associated death promoter

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Pro-apoptotic Bcl-2 protein, BAD
	complex of bcl-xl with peptide from bad
Identifiers
Symbol	Bcl-2_BAD
Pfam	PF10514
InterPro	IPR018868
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

BAD
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1G5J
Identifiers
Aliases	BAD, BBC2, BCL2L8, BCL2 associated agonist of cell death
External IDs	OMIM: 603167 MGI: 1096330 HomoloGene: 3189 GeneCards: BAD
Gene location (Human)
Chr.	Chromosome 11 (human)[1]
End	64,284,704 bp[1]
Gene location (Mouse)
Chr.	Chromosome 19 (mouse)[2]
End	6,951,899 bp[2]
RNA expression pattern
	; ;
	More reference expression data
Gene ontology
Molecular function	• 14-3-3 protein binding; • protein phosphatase binding; • GO:0001948 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; • cellular proliferation; • type B pancreatic cell proliferation; • cellular response to chromate; • extrinsic apoptotic signaling pathway via death domain receptors; • response to drug; • 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
	572
	12015
	ENSG00000002330
	ENSMUSG00000024959
	Q92934
	Q61337
	NM_032989; NM_004322
	NM_007522; NM_001285453
	NP_004313; NP_116784
	NP_001272382; NP_031548
	Wikidata
View/Edit Human	View/Edit Mouse

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:

BCL2L1,[11][12][13][14][15][16][17][18][19][20][21]
BCL2A1,[11][22]
BCL2L2,[11][15][22][23]
Bcl-2,[11][17]
MCL1[11][22]
S100A10,[24]
YWHAQ,[11][24] and
YWHAZ.[25]

References

GRCh38: Ensembl release 89: ENSG00000002330 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000024959 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
https://www.ncbi.nlm.nih.gov/gene/572#gene-expression
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.
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.
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"(
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

External links

bcl-Associated+Death+Protein at the US National Library of Medicine Medical Subject Headings (MeSH)
Human BAD genome location and BAD gene details page in the UCSC Genome Browser.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000002330 - Ensembl, May 2017

[refGRCm38Ensembl-2] 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] ttps://www.ncbi.nlm.nih.gov/gene/572#gene-expression

[adachi-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.

[sheau-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"(

[pmid15694340-11] 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.

[pmid15705582-12] 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.

[pmid9824152-13] 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.

[pmid12137781-14] 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.

[pmid12115603-15] 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.

[pmid10620799-16] 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.

[pmid7834748-17] 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.

[pmid11206074-18] 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.

[pmid11494146-19] 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.

[pmid9389483-20] 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.

[pmid11077446-21] 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.

[pmid11483855-22] 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.

[pmid10381646-23] 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.

[pmid9369453-24] 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.

[pmid11410287-25] 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.

Bcl-2-associated death promoter

Mechanism of action

Interactions

See also

References

Further reading

External links