PPM1D: Difference between revisions

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{{Infobox_gene}}
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'''Protein phosphatase 1D''' is an [[enzyme]] that in humans is encoded by the ''PPM1D'' [[gene]].<ref name="pmid9177166">{{cite journal |vauthors=Fiscella M, Zhang H, Fan S, Sakaguchi K, Shen S, Mercer WE, Vande Woude GF, O'Connor PM, Appella E | title = Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner | journal = Proc Natl Acad Sci U S A | volume = 94 | issue = 12 | pages = 6048–53 |date=July 1997 | pmid = 9177166 | pmc = 20998 | doi =10.1073/pnas.94.12.6048 | bibcode =1997PNAS...94.6048F }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PPM1D protein phosphatase 1D magnesium-dependent, delta isoform| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8493| accessdate = }}</ref>
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{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Protein phosphatase 1D magnesium-dependent, delta isoform
| HGNCid = 9277
| Symbol = PPM1D
| AltSymbols =; PP2C-DELTA; WIP1
| OMIM = 605100
| ECnumber = 
| Homologene = 31185
| MGIid = 1858214
| GeneAtlas_image1 = PBB_GE_PPM1D_204566_at_tn.png
| Function = {{GNF_GO|id=GO:0000287 |text = magnesium ion binding}} {{GNF_GO|id=GO:0004722 |text = protein serine/threonine phosphatase activity}} {{GNF_GO|id=GO:0015071 |text = protein phosphatase type 2C activity}} {{GNF_GO|id=GO:0016787 |text = hydrolase activity}} {{GNF_GO|id=GO:0030145 |text = manganese ion binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0008287 |text = protein serine/threonine phosphatase complex}}
| Process = {{GNF_GO|id=GO:0000074 |text = regulation of progression through cell cycle}} {{GNF_GO|id=GO:0000086 |text = G2/M transition of mitotic cell cycle}} {{GNF_GO|id=GO:0006470 |text = protein amino acid dephosphorylation}} {{GNF_GO|id=GO:0007049 |text = cell cycle}} {{GNF_GO|id=GO:0008285 |text = negative regulation of cell proliferation}} {{GNF_GO|id=GO:0009314 |text = response to radiation}} {{GNF_GO|id=GO:0009617 |text = response to bacterium}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 8493
    | Hs_Ensembl = ENSG00000170836
    | Hs_RefseqProtein = NP_003611
    | Hs_RefseqmRNA = NM_003620
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 56032336
    | Hs_GenLoc_end = 56096818
    | Hs_Uniprot = O15297
    | Mm_EntrezGene = 53892
    | Mm_Ensembl =   
    | Mm_RefseqmRNA = XM_001002394
    | Mm_RefseqProtein = XP_001002394
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 
    | Mm_GenLoc_start = 
    | Mm_GenLoc_end = 
    | Mm_Uniprot = 
  }}
}}
'''Protein phosphatase 1D magnesium-dependent, delta isoform''', also known as '''PPM1D''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PPM1D protein phosphatase 1D magnesium-dependent, delta isoform| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8493| accessdate = }}</ref>


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{{PBB_Summary
{{PBB_Summary
| section_title =  
| section_title =  
| summary_text = The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. The expression of this gene is induced in a p53-dependent manner in response to various environmental stresses. While being induced by tumor suppressor protein TP53/p53, this phosphatase negatively regulates the activity of p38 MAP kinase, MAPK/p38, through which it reduces the phosphorylation of p53, and in turn suppresses p53-mediated transcription and apoptosis. This phosphatase thus mediates a feedback regulation of p38-p53 signaling that contributes to growth inhibition and the suppression of stress induced apoptosis. This gene is located in a chromosomal region known to be amplified in breast cancer. The amplification of this gene has been detected in both breast cancer cell line and primary breast tumors, which suggests a role of this gene in cancer development.<ref name="entrez">{{cite web | title = Entrez Gene: PPM1D protein phosphatase 1D magnesium-dependent, delta isoform| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8493| accessdate = }}</ref>
| summary_text = The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. The expression of this gene is induced in a p53-dependent manner in response to various environmental stresses. While being induced by [[p53|tumor suppressor protein TP53/p53]], this phosphatase negatively regulates the activity of [[MAPK1|p38 MAP kinase]] (MAPK/p38) through which it reduces the phosphorylation of p53, and in turn suppresses p53-mediated transcription and apoptosis. This phosphatase thus mediates a feedback regulation of p38-p53 signaling that contributes to growth inhibition and the suppression of stress induced apoptosis. This gene is located in a chromosomal region known to be amplified in breast cancer. The amplification of this gene has been detected in both breast cancer cell line and primary breast tumors, which suggests a role of this gene in cancer development.<ref name="entrez"/>
}}
}}
==Interactions==
PPM1D has been shown to [[Protein-protein interaction|interact]] with [[CDC5L]].<ref name=pmid11101529>{{cite journal |last=Ajuh |first=P |authorlink= |author2=Kuster B |author3=Panov K |author4=Zomerdijk J C |author5=Mann M |author6=Lamond A I  |date=December 2000  |title=Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry |journal=EMBO J. |volume=19 |issue=23 |pages=6569–81 |publisher= |location = ENGLAND| issn = 0261-4189| pmid = 11101529 |doi = 10.1093/emboj/19.23.6569 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |pmc=305846 }}</ref>


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading  
{{PBB_Further_reading  
| citations =  
| citations =  
*{{cite journal | author=Adams MD, Kerlavage AR, Fleischmann RD, ''et al.'' |title=Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. |journal=Nature |volume=377 |issue= 6547 Suppl |pages= 3-174 |year= 1995 |pmid= 7566098 |doi= }}
*{{cite journal   |vauthors=Adams MD, Kerlavage AR, Fleischmann RD, etal |title=Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. |journal=Nature |volume=377 |issue= 6547 Suppl |pages= 3–174 |year= 1995 |pmid= 7566098 |doi=<!-- none available --> |url=http://www.columbia.edu/itc/biology/pollack/w4065/client_edit/readings/nature377_3.pdf | format=PDF  }}
*{{cite journal  | author=Hirano K, Ito M, Hartshorne DJ |title=Interaction of the ribosomal protein, L5, with protein phosphatase type 1. |journal=J. Biol. Chem. |volume=270 |issue= 34 |pages= 19786-90 |year= 1995 |pmid= 7649987 |doi=  }}
*{{cite journal  |vauthors=Hirano K, Ito M, Hartshorne DJ |title=Interaction of the ribosomal protein, L5, with protein phosphatase type 1. |journal=J. Biol. Chem. |volume=270 |issue= 34 |pages= 19786–90 |year= 1995 |pmid= 7649987 |doi=10.1074/jbc.270.34.19786 }}
*{{cite journal | author=Fiscella M, Zhang H, Fan S, ''et al.'' |title=Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 12 |pages= 6048-53 |year= 1997 |pmid= 9177166 |doi= }}
*{{cite journal   |vauthors=Takekawa M, Adachi M, Nakahata A, etal |title=p53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation. |journal=EMBO J. |volume=19 |issue= 23 |pages= 6517–26 |year= 2001 |pmid= 11101524 |doi= 10.1093/emboj/19.23.6517  | pmc=305857 }}
*{{cite journal | author=Takekawa M, Adachi M, Nakahata A, ''et al.'' |title=p53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation. |journal=EMBO J. |volume=19 |issue= 23 |pages= 6517-26 |year= 2001 |pmid= 11101524 |doi= 10.1093/emboj/19.23.6517 }}
*{{cite journal   |vauthors=Ajuh P, Kuster B, Panov K, etal |title=Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry. |journal=EMBO J. |volume=19 |issue= 23 |pages= 6569–81 |year= 2001 |pmid= 11101529 |doi= 10.1093/emboj/19.23.6569  | pmc=305846 }}
*{{cite journal | author=Ajuh P, Kuster B, Panov K, ''et al.'' |title=Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry. |journal=EMBO J. |volume=19 |issue= 23 |pages= 6569-81 |year= 2001 |pmid= 11101529 |doi= 10.1093/emboj/19.23.6569 }}
*{{cite journal   |vauthors=Choi J, Nannenga B, Demidov ON, etal |title=Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control. |journal=Mol. Cell. Biol. |volume=22 |issue= 4 |pages= 1094–105 |year= 2002 |pmid= 11809801 |doi=10.1128/MCB.22.4.1094-1105.2002  | pmc=134641  }}
*{{cite journal | author=Choi J, Nannenga B, Demidov ON, ''et al.'' |title=Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control. |journal=Mol. Cell. Biol. |volume=22 |issue= 4 |pages= 1094-105 |year= 2002 |pmid= 11809801 |doi= }}
*{{cite journal   |vauthors=Li J, Yang Y, Peng Y, etal |title=Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23. |journal=Nat. Genet. |volume=31 |issue= 2 |pages= 133–4 |year= 2002 |pmid= 12021784 |doi= 10.1038/ng888 }}
*{{cite journal | author=Li J, Yang Y, Peng Y, ''et al.'' |title=Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23. |journal=Nat. Genet. |volume=31 |issue= 2 |pages= 133-4 |year= 2002 |pmid= 12021784 |doi= 10.1038/ng888 }}
*{{cite journal   |vauthors=Bulavin DV, Demidov ON, Saito S, etal |title=Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity. |journal=Nat. Genet. |volume=31 |issue= 2 |pages= 210–5 |year= 2002 |pmid= 12021785 |doi= 10.1038/ng894 }}
*{{cite journal  | author=Bulavin DV, Demidov ON, Saito S, ''et al.'' |title=Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity. |journal=Nat. Genet. |volume=31 |issue= 2 |pages= 210-5 |year= 2002 |pmid= 12021785 |doi= 10.1038/ng894 }}
*{{cite journal  |vauthors=Morimoto H, Okamura H, Haneji T |title=Interaction of protein phosphatase 1 delta with nucleolin in human osteoblastic cells. |journal=J. Histochem. Cytochem. |volume=50 |issue= 9 |pages= 1187–93 |year= 2002 |pmid= 12185196 |doi= 10.1177/002215540205000905}}
*{{cite journal | author=Morimoto H, Okamura H, Haneji T |title=Interaction of protein phosphatase 1 delta with nucleolin in human osteoblastic cells. |journal=J. Histochem. Cytochem. |volume=50 |issue= 9 |pages= 1187-93 |year= 2002 |pmid= 12185196 |doi=  }}
*{{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 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |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 }}
*{{cite journal   |vauthors=Imabayashi H, Mori T, Gojo S, etal |title=Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis. |journal=Exp. Cell Res. |volume=288 |issue= 1 |pages= 35–50 |year= 2003 |pmid= 12878157 |doi=10.1016/S0014-4827(03)00130-7  }}
*{{cite journal  | author=Imabayashi H, Mori T, Gojo S, ''et al.'' |title=Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis. |journal=Exp. Cell Res. |volume=288 |issue= 1 |pages= 35-50 |year= 2003 |pmid= 12878157 |doi= }}
*{{cite journal  | author=Bernards R |title=Wip-ing out cancer. |journal=Nat. Genet. |volume=36 |issue= 4 |pages= 319–20 |year= 2004 |pmid= 15054481 |doi= 10.1038/ng0404-319 }}
*{{cite journal | author=Bernards R |title=Wip-ing out cancer. |journal=Nat. Genet. |volume=36 |issue= 4 |pages= 319-20 |year= 2004 |pmid= 15054481 |doi= 10.1038/ng0404-319 }}
*{{cite journal   |vauthors=Lu X, Bocangel D, Nannenga B, etal |title=The p53-induced oncogenic phosphatase PPM1D interacts with uracil DNA glycosylase and suppresses base excision repair. |journal=Mol. Cell |volume=15 |issue= 4 |pages= 621–34 |year= 2004 |pmid= 15327777 |doi= 10.1016/j.molcel.2004.08.007 }}
*{{cite journal | author=Lu X, Bocangel D, Nannenga B, ''et al.'' |title=The p53-induced oncogenic phosphatase PPM1D interacts with uracil DNA glycosylase and suppresses base excision repair. |journal=Mol. Cell |volume=15 |issue= 4 |pages= 621-34 |year= 2004 |pmid= 15327777 |doi= 10.1016/j.molcel.2004.08.007 }}
*{{cite journal   |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal   |vauthors=Yamaguchi H, Minopoli G, Demidov ON, etal |title=Substrate specificity of the human protein phosphatase 2Cdelta, Wip1. |journal=Biochemistry |volume=44 |issue= 14 |pages= 5285–94 |year= 2005 |pmid= 15807522 |doi= 10.1021/bi0476634 }}
*{{cite journal  | author=Yamaguchi H, Minopoli G, Demidov ON, ''et al.'' |title=Substrate specificity of the human protein phosphatase 2Cdelta, Wip1. |journal=Biochemistry |volume=44 |issue= 14 |pages= 5285-94 |year= 2005 |pmid= 15807522 |doi= 10.1021/bi0476634 }}
*{{cite journal  |vauthors=Lu X, Nannenga B, Donehower LA |title=PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. |journal=Genes Dev. |volume=19 |issue= 10 |pages= 1162–74 |year= 2005 |pmid= 15870257 |doi= 10.1101/gad.1291305  | pmc=1132003 }}
*{{cite journal | author=Lu X, Nannenga B, Donehower LA |title=PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. |journal=Genes Dev. |volume=19 |issue= 10 |pages= 1162-74 |year= 2005 |pmid= 15870257 |doi= 10.1101/gad.1291305 }}
*{{cite journal   |vauthors=Rual JF, Venkatesan K, Hao T, etal |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 |bibcode=2005Natur.437.1173R }}
*{{cite journal  | author=Rual JF, Venkatesan K, Hao T, ''et al.'' |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173-8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
*{{cite journal   |vauthors=Rauta J, Alarmo EL, Kauraniemi P, etal |title=The serine-threonine protein phosphatase PPM1D is frequently activated through amplification in aggressive primary breast tumours. |journal=Breast Cancer Res. Treat. |volume=95 |issue= 3 |pages= 257–63 |year= 2006 |pmid= 16254685 |doi= 10.1007/s10549-005-9017-7 }}
*{{cite journal | author=Rauta J, Alarmo EL, Kauraniemi P, ''et al.'' |title=The serine-threonine protein phosphatase PPM1D is frequently activated through amplification in aggressive primary breast tumours. |journal=Breast Cancer Res. Treat. |volume=95 |issue= 3 |pages= 257-63 |year= 2006 |pmid= 16254685 |doi= 10.1007/s10549-005-9017-7 }}
*{{cite journal   |vauthors=Fujimoto H, Onishi N, Kato N, etal |title=Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase. |journal=Cell Death Differ. |volume=13 |issue= 7 |pages= 1170–80 |year= 2006 |pmid= 16311512 |doi= 10.1038/sj.cdd.4401801 }}
*{{cite journal | author=Fujimoto H, Onishi N, Kato N, ''et al.'' |title=Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase. |journal=Cell Death Differ. |volume=13 |issue= 7 |pages= 1170-80 |year= 2006 |pmid= 16311512 |doi= 10.1038/sj.cdd.4401801 }}
*{{cite journal   |vauthors=Mendrzyk F, Radlwimmer B, Joos S, etal |title=Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma. |journal=J. Clin. Oncol. |volume=23 |issue= 34 |pages= 8853–62 |year= 2006 |pmid= 16314645 |doi= 10.1200/JCO.2005.02.8589 }}
*{{cite journal | author=Mendrzyk F, Radlwimmer B, Joos S, ''et al.'' |title=Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma. |journal=J. Clin. Oncol. |volume=23 |issue= 34 |pages= 8853-62 |year= 2006 |pmid= 16314645 |doi= 10.1200/JCO.2005.02.8589 }}
}}
}}
{{refend}}
{{refend}}


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Latest revision as of 19:47, 25 June 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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View/Edit Human

Protein phosphatase 1D is an enzyme that in humans is encoded by the PPM1D gene.[1][2]

The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. The expression of this gene is induced in a p53-dependent manner in response to various environmental stresses. While being induced by tumor suppressor protein TP53/p53, this phosphatase negatively regulates the activity of p38 MAP kinase (MAPK/p38) through which it reduces the phosphorylation of p53, and in turn suppresses p53-mediated transcription and apoptosis. This phosphatase thus mediates a feedback regulation of p38-p53 signaling that contributes to growth inhibition and the suppression of stress induced apoptosis. This gene is located in a chromosomal region known to be amplified in breast cancer. The amplification of this gene has been detected in both breast cancer cell line and primary breast tumors, which suggests a role of this gene in cancer development.[2]

Interactions

PPM1D has been shown to interact with CDC5L.[3]

References

  1. ↑ Fiscella M, Zhang H, Fan S, Sakaguchi K, Shen S, Mercer WE, Vande Woude GF, O'Connor PM, Appella E (July 1997). "Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner". Proc Natl Acad Sci U S A. 94 (12): 6048–53. Bibcode:1997PNAS...94.6048F. doi:10.1073/pnas.94.12.6048. PMC 20998. PMID 9177166.
  2. ↑ 2.0 2.1 "Entrez Gene: PPM1D protein phosphatase 1D magnesium-dependent, delta isoform".
  3. ↑ Ajuh, P; Kuster B; Panov K; Zomerdijk J C; Mann M; Lamond A I (December 2000). "Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry". EMBO J. ENGLAND. 19 (23): 6569–81. doi:10.1093/emboj/19.23.6569. ISSN 0261-4189. PMC 305846. PMID 11101529.

Further reading



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