View source for PPP1R15A

{{Short description|Protein found in humans}}
{{Infobox_gene}}
'''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]].<ref name="pmid9153226">{{cite journal | vauthors = Hollander MC, Zhan Q, Bae I, ((Fornace AJ Jr)) | title = Mammalian GADD34, an apoptosis- and DNA damage-inducible gene | journal = J Biol Chem | volume = 272 | issue = 21 | pages = 13731–7 |date=Jul 1997 | pmid = 9153226 | doi =10.1074/jbc.272.21.13731  | doi-access =  free}}</ref><ref name="pmid9413226">{{cite journal | vauthors = Korabiowska M, Betke H, Kellner S, Stachura J, Schauer A | title = Differential expression of growth arrest, DNA damage genes and tumour suppressor gene p53 in naevi and malignant melanomas | journal = Anticancer Res | volume = 17 | issue = 5A | pages = 3697–700 |date=Jan 1998 | pmid = 9413226 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PPP1R15A protein phosphatase 1, regulatory (inhibitor) subunit 15A| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23645}}</ref>
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.<ref name="pmid8139541">{{cite journal | vauthors = Zhan Q, Lord KA, Alamo I, Hollander MC, Carrier F, Ron D, Kohn KW, Hoffman B, Liebermann DA, Fornace AJ | title = The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth | journal = Mol. Cell. Biol. | volume = 14 | issue = 4 | pages = 2361–71 |date=April 1994 | pmid = 8139541 | pmc = 358603 | doi = 10.1128/mcb.14.4.2361}}</ref> Later on it has been characterized as a gene playing a role in [[endoplasmic reticulum|ER]] stress-induced cell death, being a target of [[ATF4]] that plays a role in ER-mediated cell death via promoting protein [[dephosphorylation]] of [[eIF2]]α and reversing translational inhibition.<ref name="pmid23850759">{{cite journal | vauthors = Sano R, Reed JC | title = ER stress-induced cell death mechanisms | journal = Biochim. Biophys. Acta | volume = 1833| issue = 12| pages = 3460–70|date=July 2013 | pmid = 23850759 | doi = 10.1016/j.bbamcr.2013.06.028 | pmc=3834229}}</ref>
== 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.<ref name="entrez"/>
==Interactions==
PPP1R15A has been shown to [[Protein-protein interaction|interact]] with:
* [[BAG1]]<ref name = pmid12724406/>
* [[LYN]],<ref name = pmid11517336>{{cite journal | vauthors = Grishin AV, Azhipa O, Semenov I, Corey SJ | title = Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 18 | pages = 10172–7 | year = 2001 | pmid = 11517336 | pmc = 56934 | doi = 10.1073/pnas.191130798 | bibcode = 2001PNAS...9810172G | doi-access = free }}</ref>
* [[MLL (gene)|MLL]],<ref name = pmid10490642/>
* [[PPP1CA]],<ref name = pmid12724406>{{cite journal | vauthors = Hung WJ, Roberson RS, Taft J, Wu DY | title = Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions | journal = Mol. Cell. Biol. | volume = 23 | issue = 10 | pages = 3477–86 | year = 2003 | pmid = 12724406 | pmc = 164759 | doi = 10.1128/MCB.23.10.3477-3486.2003}}</ref><ref name = pmid12016208/><ref name = pmid11564868/>
* [[PPP1CB]],<ref name = pmid12016208>{{cite journal | vauthors = Wu DY, Tkachuck DC, Roberson RS, Schubach WH | title = 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 | journal = J. Biol. Chem. | volume = 277 | issue = 31 | pages = 27706–15 | year = 2002 | pmid = 12016208 | doi = 10.1074/jbc.M200955200 | doi-access = free }}</ref><ref name = pmid11564868>{{cite journal | vauthors = Connor JH, Weiser DC, Li S, Hallenbeck JM, Shenolikar S | title = Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1 | journal = Mol. Cell. Biol. | volume = 21 | issue = 20 | pages = 6841–50 | year = 2001 | pmid = 11564868 | pmc = 99861 | doi = 10.1128/MCB.21.20.6841-6850.2001 }}</ref>
* [[PPP1CC]],<ref name = pmid12016208/><ref name = pmid11564868/>
* [[SMARCB1]],<ref name = pmid10490642>{{cite journal | vauthors = Adler HT, Chinery R, Wu DY, Kussick SJ, Payne JM, Fornace AJ, Tkachuk DC | title = Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins | journal = Mol. Cell. Biol. | volume = 19 | issue = 10 | pages = 7050–60 | year = 1999 | pmid = 10490642 | pmc = 84700 | doi = 10.1128/mcb.19.10.7050}}</ref><ref name = pmid12016208/> and
* [[TSN (gene)|TSN]].<ref name = pmid10434033>{{cite journal | vauthors = Hasegawa T, Isobe K | title = Evidence for the interaction between Translin and GADD34 in mammalian cells | journal = Biochim. Biophys. Acta | volume = 1428 | issue = 2–3 | pages = 161–8 | year = 1999 | pmid = 10434033 | doi = 10.1016/s0304-4165(99)00060-4}}</ref>
==References==
{{Reflist}}
==Further reading==
{{refbegin | 2}}
*{{cite journal  | vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1–2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8  }}
*{{cite journal   |vauthors=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1–2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3  }}
*{{cite journal  | vauthors=Hasegawa T, Isobe K |title=Evidence for the interaction between Translin and GADD34 in mammalian cells. |journal=Biochim. Biophys. Acta |volume=1428 |issue= 2–3 |pages= 161–8 |year= 1999 |pmid= 10434033 |doi=  10.1016/s0304-4165(99)00060-4}}
*{{cite journal   |vauthors=Adler HT, Chinery R, Wu DY, etal |title=Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins. |journal=Mol. Cell. Biol. |volume=19 |issue= 10 |pages= 7050–60 |year= 2000 |pmid= 10490642 |doi=  10.1128/mcb.19.10.7050| pmc=84700  }}
*{{cite journal  | vauthors=Hasegawa T, Yagi A, Isobe K |title=Interaction between GADD34 and kinesin superfamily, KIF3A. |journal=Biochem. Biophys. Res. Commun. |volume=267 |issue= 2 |pages= 593–6 |year= 2000 |pmid= 10631107 |doi= 10.1006/bbrc.1999.1991 }}
*{{cite journal  | vauthors=Hasegawa T, Xiao H, Hamajima F, Isobe K |title=Interaction between DNA-damage protein GADD34 and a new member of the Hsp40 family of heat shock proteins that is induced by a DNA-damaging reagent. |journal=Biochem. J. |volume=352 |issue=  3|pages= 795–800 |year= 2001 |pmid= 11104688 |doi=  10.1042/0264-6021:3520795| pmc=1221519  }}
*{{cite journal  | vauthors=Grishin AV, Azhipa O, Semenov I, Corey SJ |title=Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue= 18 |pages= 10172–7 |year= 2001 |pmid= 11517336 |doi= 10.1073/pnas.191130798  | pmc=56934 |bibcode=2001PNAS...9810172G |doi-access=free }}
*{{cite journal   |vauthors=Connor JH, Weiser DC, Li S, etal |title=Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1. |journal=Mol. Cell. Biol. |volume=21 |issue= 20 |pages= 6841–50 |year= 2001 |pmid= 11564868 |doi= 10.1128/MCB.21.20.6841-6850.2001  | pmc=99861 }}
*{{cite journal  | vauthors=Wu DY, Tkachuck DC, Roberson RS, Schubach WH |title=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. |journal=J. Biol. Chem. |volume=277 |issue= 31 |pages= 27706–15 |year= 2002 |pmid= 12016208 |doi= 10.1074/jbc.M200955200 |doi-access= free }}
*{{cite journal  | vauthors=Korabiowska M, Cordon-Cardo C, Betke H  | author2-link=Carlos Cordon-Cardo  |title=GADD153 is an independent prognostic factor in melanoma: immunohistochemical and molecular genetic analysis. |journal=Histol. Histopathol. |volume=17 |issue= 3 |pages= 805–11 |year= 2003 |pmid= 12168790 |display-authors=etal}}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }}
*{{cite journal  | vauthors=Brush MH, Weiser DC, Shenolikar S |title=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. |journal=Mol. Cell. Biol. |volume=23 |issue= 4 |pages= 1292–303 |year= 2003 |pmid= 12556489 |doi=10.1128/MCB.23.4.1292-1303.2003  | pmc=141149  }}
*{{cite journal  | vauthors=Hung WJ, Roberson RS, Taft J, Wu DY |title=Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions. |journal=Mol. Cell. Biol. |volume=23 |issue= 10 |pages= 3477–86 |year= 2003 |pmid= 12724406 |doi=10.1128/MCB.23.10.3477-3486.2003  | pmc=164759  }}
*{{cite journal  | vauthors=Hollander MC, Poola-Kella S, Fornace AJ |title=Gadd34 functional domains involved in growth suppression and apoptosis. |journal=Oncogene |volume=22 |issue= 25 |pages= 3827–32 |year= 2003 |pmid= 12813455 |doi= 10.1038/sj.onc.1206567 |s2cid=27555253 |doi-access=  }}
*{{cite journal  | vauthors=Powolny A, Takahashi K, Hopkins RG, Loo G |title=Induction of GADD gene expression by phenethylisothiocyanate in human colon adenocarcinoma cells. |journal=J. Cell. Biochem. |volume=90 |issue= 6 |pages= 1128–39 |year= 2004 |pmid= 14635187 |doi= 10.1002/jcb.10733 |s2cid=33081723 |url=http://libres.uncg.edu/ir/uncg/f/G_Loo_Induction_2003.pdf }}
*{{cite journal   |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 |doi-access= free }}
*{{cite journal   |vauthors=Shi W, Sun C, He B, etal |title=GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. |journal=J. Cell Biol. |volume=164 |issue= 2 |pages= 291–300 |year= 2004 |pmid= 14718519 |doi= 10.1083/jcb.200307151  | pmc=2172339 }}
*{{cite journal   |vauthors=Colland F, Jacq X, Trouplin V, etal |title=Functional proteomics mapping of a human signaling pathway. |journal=Genome Res. |volume=14 |issue= 7 |pages= 1324–32 |year= 2004 |pmid= 15231748 |doi= 10.1101/gr.2334104  | pmc=442148 }}
{{refend}}