PPP1R15A
Protein phosphatase 1 regulatory subunit 15A also known as growth arrest and DNA damage-inducible protein GADD34 is a protein that in humans is encoded by the PPP1R15A gene.[5][6][7]
The Gadd34/MyD116 gene was originally discovered as a member in a set of gadd and MyD mammalian genes encoding acidic proteins that synergistically suppress cell growth.[8] Later on it has been characterized as a gene playing a role in ER stress-induced cell death, being a target of ATF4 that plays a role in ER-mediated cell death via promoting protein dephosphorylation of eIF2α and reversing translational inhibition.[9]
Function
This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The induction of this gene by ionizing radiation occurs in certain cell lines regardless of p53 status, and its protein response is correlated with apoptosis following ionizing radiation.[7]
Interactions
PPP1R15A has been shown to interact with:
- BAG1[10]
- LYN,[11]
- MLL,[12]
- PPP1CA,[10][13][14]
- PPP1CB,[13][14]
- PPP1CC,[13][14]
- SMARCB1,[12][13] and
- TSN.[15]
Further reading
- 1 2 3 GRCh38: Ensembl release 89: ENSG00000087074 - Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000040435 - Ensembl, May 2017
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- ↑ Hollander MC, Zhan Q, Bae I, Fornace AJ Jr (Jul 1997). "Mammalian GADD34, an apoptosis- and DNA damage-inducible gene". J Biol Chem. 272 (21): 13731–7. PMID 9153226. doi:10.1074/jbc.272.21.13731.
- ↑ Korabiowska M, Betke H, Kellner S, Stachura J, Schauer A (Jan 1998). "Differential expression of growth arrest, DNA damage genes and tumour suppressor gene p53 in naevi and malignant melanomas". Anticancer Res. 17 (5A): 3697–700. PMID 9413226.
- 1 2 "Entrez Gene: PPP1R15A protein phosphatase 1, regulatory (inhibitor) subunit 15A".
- ↑ Zhan Q, Lord KA, Alamo I, Hollander MC, Carrier F, Ron D, Kohn KW, Hoffman B, Liebermann DA, Fornace AJ (April 1994). "The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth". Mol. Cell. Biol. 14 (4): 2361–71. PMC 358603 . PMID 8139541. doi:10.1128/mcb.14.4.2361.
- ↑ Sano R, Reed JC (July 2013). "ER stress-induced cell death mechanisms". Biochim. Biophys. Acta. 1833 (12): 3460–70. PMC 3834229 . PMID 23850759. doi:10.1016/j.bbamcr.2013.06.028.
- 1 2 Hung WJ, Roberson RS, Taft J, Wu DY (2003). "Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions". Mol. Cell. Biol. 23 (10): 3477–86. PMC 164759 . PMID 12724406. doi:10.1128/MCB.23.10.3477-3486.2003.
- ↑ Grishin AV, Azhipa O, Semenov I, Corey SJ (2001). "Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis". Proc. Natl. Acad. Sci. U.S.A. 98 (18): 10172–7. PMC 56934 . PMID 11517336. doi:10.1073/pnas.191130798.
- 1 2 Adler HT, Chinery R, Wu DY, Kussick SJ, Payne JM, Fornace AJ, Tkachuk DC (1999). "Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins". Mol. Cell. Biol. 19 (10): 7050–60. PMC 84700 . PMID 10490642. doi:10.1128/mcb.19.10.7050.
- 1 2 3 4 Wu DY, Tkachuck DC, Roberson RS, Schubach WH (2002). "The human SNF5/INI1 protein facilitates the function of the growth arrest and DNA damage-inducible protein (GADD34) and modulates GADD34-bound protein phosphatase-1 activity". J. Biol. Chem. 277 (31): 27706–15. PMID 12016208. doi:10.1074/jbc.M200955200.
- 1 2 3 Connor JH, Weiser DC, Li S, Hallenbeck JM, Shenolikar S (2001). "Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1". Mol. Cell. Biol. 21 (20): 6841–50. PMC 99861 . PMID 11564868. doi:10.1128/MCB.21.20.6841-6850.2001.
- ↑