Protein Phosphatase 1, Regulatory Subunit 15A (PPP1R15A)

PPP1-R15A; PPP1R15-A; PPP1-R15-A; GADD34; Growth Arrest And DNA-Damage-Inducible 34; Myeloid differentiation primary response protein MyD116 homolog

SPN	U645
HGNC	14375
MGI	1927072
PubMed	22315398
RGD	621526
UniProt	O75807
Wiki	PPP1R15A

Protein phosphatase 1 regulatory subunit 15A 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.

The predicted 674-amino acid protein is highly negatively charged and contains 4 central 34-residue repeats. It shares 52 to 55% amino acid identity with its rodent homologs. In addition, the C terminus of GADD34 shares significant homology with the C terminus of ICP34.5, an apoptosis inhibition protein of herpes simplex virus (HSV)-1.

Reference

"Mammalian GADD34, an apoptosis- and DNA damage-inducible gene."
J. Biol. Chem. 272:13731-13737(1997) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth."
Mol. Cell. Biol. 14:2361-2371(1994) [PubMed] [Europe PMC] [Abstract]

"Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins."
Mol. Cell. Biol. 19:7050-7060(1999) [PubMed] [Europe PMC] [Abstract]

"Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis."
Proc. Natl. Acad. Sci. U.S.A. 98:10172-10177(2001) [PubMed] [Europe PMC] [Abstract]

"Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1."
Mol. Cell. Biol. 21:6841-6850(2001) [PubMed] [Europe PMC] [Abstract]

"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. 277:27706-27715(2002) [PubMed] [Europe PMC] [Abstract]

"mda-7 (IL-24) Mediates selective apoptosis in human melanoma cells by inducing the coordinated overexpression of the GADD family of genes by means of p38 MAPK."
Proc. Natl. Acad. Sci. U.S.A. 99:10054-10059(2002) [PubMed] [Europe PMC] [Abstract]

"GADD34 induces p53 phosphorylation and p21/WAF1 transcription."
J. Cell. Biochem. 90:1242-1249(2003) [PubMed] [Europe PMC] [Abstract]

"Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2."
Mol. Cell. Biol. 23:1292-1303(2003) [PubMed] [Europe PMC] [Abstract]

"Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions."
Mol. Cell. Biol. 23:3477-3486(2003) [PubMed] [Europe PMC] [Abstract]

"GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor."
J. Cell Biol. 164:291-300(2004) [PubMed] [Europe PMC] [Abstract]

"A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress."
Science 307:935-939(2005) [PubMed] [Europe PMC] [Abstract]

"Association with endoplasmic reticulum promotes proteasomal degradation of GADD34 protein."
J. Biol. Chem. 286:21687-21696(2011) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation at tyrosine 262 promotes GADD34 protein turnover."
J. Biol. Chem. 288:33146-33155(2013) [PubMed] [Europe PMC] [Abstract]