PPM1D

Summary

Gene Symbol: PPM1D
Description: protein phosphatase, Mg2+/Mn2+ dependent 1D
Alias: IDDGIP, PP2C-DELTA, WIP1, protein phosphatase 1D, protein phosphatase 1D magnesium-dependent, delta isoform, protein phosphatase 2C delta isoform, protein phosphatase Wip1, wild-type p53-induced phosphatase 1
Species: human
Products:     PPM1D

Top Publications

  1. Mendrzyk F, Radlwimmer B, Joos S, Kokocinski F, Benner A, Stange D, et al. Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma. J Clin Oncol. 2005;23:8853-62 pubmed
    ..2, two of the most frequently gained chromosomal regions, confined amplicons were identified that contained the PPM1D and CDK6 genes, respectively...
  2. Ali A, Abedini M, Tsang B. The oncogenic phosphatase PPM1D confers cisplatin resistance in ovarian carcinoma cells by attenuating checkpoint kinase 1 and p53 activation. Oncogene. 2012;31:2175-86 pubmed publisher
    ..Although the oncogenic phosphatase protein phosphatase magnesium-dependent 1 (PPM1D) can deactivate both p53 and Chk1 through site-specific dephosphorylation, whether PPM1D has a role in CDDP ..
  3. Hershko T, Korotayev K, Polager S, Ginsberg D. E2F1 modulates p38 MAPK phosphorylation via transcriptional regulation of ASK1 and Wip1. J Biol Chem. 2006;281:31309-16 pubmed
    ..E2F-dependent down-regulation of the p38 signaling pathway is achieved through E2F-induced up-regulation of Wip1, a phosphatase that dephosphorylates and inactivates p38...
  4. Yoda A, Xu X, Onishi N, Toyoshima K, Fujimoto H, Kato N, et al. Intrinsic kinase activity and SQ/TQ domain of Chk2 kinase as well as N-terminal domain of Wip1 phosphatase are required for regulation of Chk2 by Wip1. J Biol Chem. 2006;281:24847-62 pubmed
    ..Recently, we have shown that Chk2 associates with the oncogenic Wip1 (PPM1D) phosphatase and that Wip1 acts as a negative regulator of Chk2 during DNA damage response by dephosphorylating ..
  5. Fuku T, Semba S, Yutori H, Yokozaki H. Increased wild-type p53-induced phosphatase 1 (Wip1 or PPM1D) expression correlated with downregulation of checkpoint kinase 2 in human gastric carcinoma. Pathol Int. 2007;57:566-71 pubmed
    ..The purpose of the present paper was to investigate the expression of wild-type p53-induced phosphatase 1 (Wip1 or PPM1D), a negative regulator of Chk2, to better understand its role in human gastric cancer...
  6. Yamaguchi H, Durell S, Chatterjee D, Anderson C, Appella E. The Wip1 phosphatase PPM1D dephosphorylates SQ/TQ motifs in checkpoint substrates phosphorylated by PI3K-like kinases. Biochemistry. 2007;46:12594-603 pubmed
    The wild-type p53-induced phosphatase Wip1 (PP2Cdelta or PPM1D) is a member of the protein phosphatase 2C (PP2C) family and controls cell cycle checkpoints in response to DNA damage...
  7. Chew J, Biswas S, Shreeram S, Humaidi M, Wong E, Dhillion M, et al. WIP1 phosphatase is a negative regulator of NF-kappaB signalling. Nat Cell Biol. 2009;11:659-66 pubmed publisher
    ..By using a genome-scale siRNA screen, we identified the WIP1 phosphatase as a negative regulator of NF-kappaB signalling...
  8. Lu X, Bocangel D, Nannenga B, Yamaguchi H, Appella E, Donehower L. The p53-induced oncogenic phosphatase PPM1D interacts with uracil DNA glycosylase and suppresses base excision repair. Mol Cell. 2004;15:621-34 pubmed
    The wild-type p53-induced phosphatase PPM1D (or Wip1) is a serine/threonine phosphatase that is transcriptionally upregulated by p53 following ultraviolet and ionizing radiation...
  9. Goloudina A, Tanoue K, Hammann A, Fourmaux E, Le Guezennec X, Bulavin D, et al. Wip1 promotes RUNX2-dependent apoptosis in p53-negative tumors and protects normal tissues during treatment with anticancer agents. Proc Natl Acad Sci U S A. 2012;109:E68-75 pubmed publisher
    ..Here we show that a previously proposed strategy directed to Wip1 inhibition could be ineffective in tumors lacking p53...

More Information

Publications83

  1. Bulavin D, Demidov O, Saito S, Kauraniemi P, Phillips C, Amundson S, et al. Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity. Nat Genet. 2002;31:210-5 pubmed
    ..Activity of p38 MAPK is regulated by the p53-inducible phosphatase PPM1D, creating a potential feedback loop...
  2. Liang C, Guo E, Lu S, Wang S, Kang C, Chang L, et al. Over-expression of wild-type p53-induced phosphatase 1 confers poor prognosis of patients with gliomas. Brain Res. 2012;1444:65-75 pubmed publisher
    Wild-type p53-induced phosphatase 1 (Wip1) is a member of the protein phosphatase 2C family, which is characterized by distinctive oncogenic properties...
  3. Takekawa M, Adachi M, Nakahata A, Nakayama I, Itoh F, Tsukuda H, et al. p53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation. EMBO J. 2000;19:6517-26 pubmed
    ..Here we report that a member of the protein phosphatase type 2C family, Wip1, has a role in down-regulating p38-p53 signaling during the recovery phase of the damaged cells...
  4. Dudgeon C, Shreeram S, Tanoue K, Mazur S, Sayadi A, Robinson R, et al. Genetic variants and mutations of PPM1D control the response to DNA damage. Cell Cycle. 2013;12:2656-64 pubmed publisher
    ..On the other hand, in primary human cancers, PPM1D mutations commonly result in a gain-of-function phenotype, leading us to identify a hot-spot truncating mutation ..
  5. Yagi H, Chuman Y, Kozakai Y, Imagawa T, Takahashi Y, Yoshimura F, et al. A small molecule inhibitor of p53-inducible protein phosphatase PPM1D. Bioorg Med Chem Lett. 2012;22:729-32 pubmed publisher
    b>PPM1D is a p53-inducible Ser/Thr protein phosphatase. PPM1D gene amplification and overexpression have been reported in a variety of human tumors, including breast cancer and neuroblastoma...
  6. Fiscella M, Zhang H, Fan S, Sakaguchi K, Shen S, Mercer W, et al. 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. 1997;94:6048-53 pubmed
    ..We have named this novel gene, wip1. In vitro, recombinant Wip1 displayed characteristics of a type 2C phosphatase, including Mg2+ dependence and ..
  7. Satoh N, Maniwa Y, Bermudez V, Nishimura K, Nishio W, Yoshimura M, et al. Oncogenic phosphatase Wip1 is a novel prognostic marker for lung adenocarcinoma patient survival. Cancer Sci. 2011;102:1101-6 pubmed publisher
    DNA damage response pathways are important for maintaining genomic stability. The oncogenic phosphatase Wip1 plays a crucial role in DNA damage response by inhibiting several cell cycle proteins, including p53...
  8. Lambros M, Natrajan R, Geyer F, Lopez Garcia M, Dedes K, Savage K, et al. PPM1D gene amplification and overexpression in breast cancer: a qRT-PCR and chromogenic in situ hybridization study. Mod Pathol. 2010;23:1334-45 pubmed publisher
    b>PPM1D (protein phosphatase magnesium-dependent 1?) maps to the 17q23.2 amplicon and is amplified in ?8% of breast cancers...
  9. Kleiblova P, Shaltiël I, Benada J, Sevcik J, Pecháčková S, Pohlreich P, et al. Gain-of-function mutations of PPM1D/Wip1 impair the p53-dependent G1 checkpoint. J Cell Biol. 2013;201:511-21 pubmed publisher
    ..The serine/threonine phosphatase PPM1D/Wip1 inactivates p53 and promotes termination of the DDR pathway...
  10. Oliva Trastoy M, Berthonaud V, Chevalier A, Ducrot C, Marsolier Kergoat M, Mann C, et al. The Wip1 phosphatase (PPM1D) antagonizes activation of the Chk2 tumour suppressor kinase. Oncogene. 2007;26:1449-58 pubmed
    ..The oncogenic protein Wip1, a PP2C phosphatase, binds Chk2 and dephosphorylates phospho-Thr68...
  11. Yu E, Ahn Y, Jang S, Kim M, Yoon H, Gong G, et al. Overexpression of the wip1 gene abrogates the p38 MAPK/p53/Wip1 pathway and silences p16 expression in human breast cancers. Breast Cancer Res Treat. 2007;101:269-78 pubmed
    Wild-type p53-induced phosphatase (Wip1 or PPM1D) is a serine/threonine protein phosphatase expressed under various stress conditions, which selectively inactivates p38 MAPK...
  12. Choi J, Nannenga B, Demidov O, Bulavin D, Cooney A, Brayton C, et al. Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control. Mol Cell Biol. 2002;22:1094-105 pubmed
    The Wip1 gene is a serine/threonine phosphatase that is induced in a p53-dependent manner by DNA-damaging agents...
  13. Yamaguchi H, Minopoli G, Demidov O, Chatterjee D, Anderson C, Durell S, et al. Substrate specificity of the human protein phosphatase 2Cdelta, Wip1. Biochemistry. 2005;44:5285-94 pubmed
    b>Wip1, the wild-type p53-induced phosphatase, selectively dephosphorylates a threonine residue on p38 MAPK and mediates a negative feedback loop of the p38 MAPK-p53 signaling pathway...
  14. Rauta J, Alarmo E, Kauraniemi P, Karhu R, Kuukasjärvi T, Kallioniemi A. The serine-threonine protein phosphatase PPM1D is frequently activated through amplification in aggressive primary breast tumours. Breast Cancer Res Treat. 2006;95:257-63 pubmed
    The serine-threonine protein phosphatase PPM1D is likely to play an important role in tumorigenesis...
  15. Pärssinen J, Alarmo E, Khan S, Karhu R, Vihinen M, Kallioniemi A. Identification of differentially expressed genes after PPM1D silencing in breast cancer. Cancer Lett. 2008;259:61-70 pubmed
    Amplification and overexpression of PPM1D (protein phosphatase magnesium-dependent 1 delta) has been observed in various cancer cell lines and primary tumors and has also been associated with cancers of poor prognosis...
  16. Pärssinen J, Alarmo E, Karhu R, Kallioniemi A. PPM1D silencing by RNA interference inhibits proliferation and induces apoptosis in breast cancer cell lines with wild-type p53. Cancer Genet Cytogenet. 2008;182:33-9 pubmed publisher
    b>PPM1D is an oncogene that is amplified and overexpressed in many human tumors, including breast cancer...
  17. Yoda A, Toyoshima K, Watanabe Y, Onishi N, Hazaka Y, Tsukuda Y, et al. Arsenic trioxide augments Chk2/p53-mediated apoptosis by inhibiting oncogenic Wip1 phosphatase. J Biol Chem. 2008;283:18969-79 pubmed publisher
    The oncogenic Wip1 phosphatase (PPM1D) is induced upon DNA damage in a p53-dependent manner and is required for inactivation or suppression of DNA damage-induced cell cycle checkpoint arrest and of apoptosis by dephosphorylating and ..
  18. Li J, Yang Y, Peng Y, Austin R, Van Eyndhoven W, Nguyen K, et al. Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23. Nat Genet. 2002;31:133-4 pubmed
    We found that PPM1D, encoding a serine/threonine protein phosphatase, lies within an epicenter of the region at 17q23 that is amplified in breast cancer...
  19. Wang P, Rao J, Yang H, Zhao H, Yang L. PPM1D silencing by lentiviral-mediated RNA interference inhibits proliferation and invasion of human glioma cells. J Huazhong Univ Sci Technolog Med Sci. 2011;31:94-99 pubmed publisher
    To construct a lentiviral shRNA vector targeting human protein phosphatase 1D magnesium-dependent (PPM1D) gene and detect its effectiveness of gene silencing in human gliomas, specific siRNA targets with short hairpin frame were designed ..
  20. Lu X, Nannenga B, Donehower L. PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Genes Dev. 2005;19:1162-74 pubmed
    ..Here we show that the oncogenic p53-induced serine/threonine phosphatase, PPM1D (or Wip1), dephosphorylates two ATM/ATR targets, Chk1 and p53...
  21. Lindqvist A, de Bruijn M, Macurek L, Bras A, Mensinga A, Bruinsma W, et al. Wip1 confers G2 checkpoint recovery competence by counteracting p53-dependent transcriptional repression. EMBO J. 2009;28:3196-206 pubmed publisher
    ..Here, we identify the phosphatase Wip1 (PPM1D) as a factor that maintains a cell competent for cell-cycle re-entry during an ongoing DNA damage response in G2...
  22. Shreeram S, Demidov O, Hee W, Yamaguchi H, Onishi N, Kek C, et al. Wip1 phosphatase modulates ATM-dependent signaling pathways. Mol Cell. 2006;23:757-64 pubmed
    Deletion of Ppm1d, the gene encoding the Wip1 phosphatase, renders cells resistant to transformation and mice resistant to tumor development...
  23. Choi D, Na W, Kabir M, Yi E, Kwon S, Yeom J, et al. WIP1, a homeostatic regulator of the DNA damage response, is targeted by HIPK2 for phosphorylation and degradation. Mol Cell. 2013;51:374-85 pubmed publisher
    b>WIP1 (wild-type p53-induced phosphatase 1) functions as a homeostatic regulator of the ataxia telangiectasia mutated (ATM)-mediated signaling pathway in response to ionizing radiation (IR)...
  24. Li G, Zhang X, Yuan L, Jiao Q, Liu D, Liu J. Protein phosphatase magnesium-dependent 1? (PPM1D) mRNA expression is a prognosis marker for hepatocellular carcinoma. PLoS ONE. 2013;8:e60775 pubmed publisher
    Protein phosphatase magnesium-dependent 1? (PPM1D) is an oncogene, overexpressed in many solid tumors, including ovarian cancer and breast cancer...
  25. Ruark E, Snape K, Humburg P, Loveday C, Bajrami I, Brough R, et al. Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer. Nature. 2013;493:406-10 pubmed publisher
    ..replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer...
  26. Rossi M, Demidov O, Anderson C, Appella E, Mazur S. Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites. Nucleic Acids Res. 2008;36:7168-80 pubmed publisher
    b>PPM1D (Wip1), a type PP2C phosphatase, is expressed at low levels in most normal tissues but is overexpressed in several types of cancers...
  27. Moon S, Lin L, Zhang X, Nguyen T, Darlington Y, Waldman A, et al. Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-H2AX and suppresses DNA double strand break repair. J Biol Chem. 2010;285:12935-47 pubmed publisher
    ..Here, we demonstrate that the wild-type p53-induced phosphatase 1 (WIP1) also dephosphorylates gamma-H2AX at serine 139 in vitro and in vivo...
  28. Macurek L, Lindqvist A, Voets O, Kool J, Vos H, Medema R. Wip1 phosphatase is associated with chromatin and dephosphorylates gammaH2AX to promote checkpoint inhibition. Oncogene. 2010;29:2281-91 pubmed publisher
    ..In this study, we show that the DNA damage-responsive Wip1 phosphatase is bound to chromatin...
  29. Fujimoto H, Onishi N, Kato N, Takekawa M, Xu X, Kosugi A, et al. Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase. Cell Death Differ. 2006;13:1170-80 pubmed
    ..Here we show that Chk2 associates with the oncogenic protein Wip1 (wild-type p53-inducible phosphatase 1) (PPM1D), a p53-inducible protein phosphatase...
  30. Song J, Ryu S, Cho Y, Kim Y, Lee B, Lee S, et al. Wip1 suppresses apoptotic cell death through direct dephosphorylation of BAX in response to ?-radiation. Cell Death Dis. 2013;4:e744 pubmed publisher
    Wild-type p53-induced phosphatase 1 (Wip1) is a p53-inducible serine/threonine phosphatase that switches off DNA damage checkpoint responses by the dephosphorylation of certain proteins (i.e...
  31. Lu X, Ma O, Nguyen T, Jones S, Oren M, Donehower L. The Wip1 Phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop. Cancer Cell. 2007;12:342-54 pubmed
    ..Here we show that the wild-type p53-induced phosphatase 1 (Wip1), or PPM1D, downregulates p53 protein levels by stabilizing Mdm2 and facilitating its access to p53...
  32. Liu K, Zhang H, Wang Y, Wang L, Chen H, Long C, et al. Wild-type p53-induced Phosphatase 1 Deficiency Exacerbates Myocardial Infarction-induced Ischemic Injury. Chin Med J (Engl). 2017;130:1333-1341 pubmed publisher
    Myocardial infarction (MI) is a major disease burden. Wild-type p53-induced phosphatase 1 (Wip1) has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wip1 in cardiac ..
  33. Wang H, Liu Z, Qiu L, Guo J, Li Y, Zhang J, et al. Knockdown of Wip1 Enhances Sensitivity to Radiation in HeLa Cells Through Activation of p38 MAPK. Oncol Res. 2014;22:225-33 pubmed publisher
    ..of the study were to investigate the functional role and potential mechanism of wild-type p53-induced phosphatase (Wip1) in cervical cancer cell line HeLa cells, along with the effect of knockdown of Wip1 in combination with γ-..
  34. Lowe J, Cha H, Lee M, Mazur S, Appella E, Fornace A. Regulation of the Wip1 phosphatase and its effects on the stress response. Front Biosci (Landmark Ed). 2012;17:1480-98 pubmed
    Wip1 (PPM1D) is a stress responsive PP2C phosphatase that plays a key role in stress signaling...
  35. Yang D, He J, Li J, Ma W, Hu X, Xin S, et al. [Expression of proto-oncogene Wip1 in breast cancer and its clinical significance]. Zhonghua Yi Xue Za Zhi. 2010;90:519-22 pubmed
    To investigate the expression of proto-oncogene Wip1 in breast cancer tissue and its clinical significance...
  36. Zhen H, Zhao L, Ling Z, Kuo L, Xue X, Feng J. Wip1 regulates blood-brain barrier function and neuro-inflammation induced by lipopolysaccharide via the sonic hedgehog signaling signaling pathway. Mol Immunol. 2018;93:31-37 pubmed publisher
    The blood brain barrier (BBB) is a diffusion barrier that maintains the brain environment. Wip1 is a nuclear phosphatase induced by many factors and involved in various stresses, tumorigenesis, organismal aging, and neurogenesis...
  37. Li D, Zhang L, Huang X, Liu L, He Y, Xu L, et al. WIP1 Phosphatase Plays a Critical Neuroprotective Role in Brain Injury Induced by High-Altitude Hypoxic Inflammation. Neurosci Bull. 2017;33:292-298 pubmed publisher
    ..The phosphatase wild-type p53-induced phosphatase 1 (WIP1) plays important roles in various physiological and pathological processes, including the regulation of ..
  38. Clausse V, Goloudina A, Uyanik B, Kochetkova E, Richaud S, Fedorova O, et al. Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy. Cell Death Dis. 2016;7:e2195 pubmed publisher
    ..We have previously shown that overexpression of the phosphatase Wip1 in p53-negative tumors sensitizes them to chemotherapeutic agents, while protecting normal tissues from the side ..
  39. Fukami S, Riemenschneider M, Kohno M, Steiger H. Expression and gene doses changes of the p53-regulator PPM1D in meningiomas: a role in meningioma progression?. Brain Tumor Pathol. 2016;33:191-9 pubmed publisher
    The aim of our study was to clarify the expression and gene copy number levels of protein phosphatase 1D magnesium-dependent, delta isoform (PPM1D), which is thought to be a regulator of the p53 protein in meningiomas of all three ..
  40. Pharoah P, Song H, Dicks E, Intermaggio M, Harrington P, Baynes C, et al. PPM1D Mosaic Truncating Variants in Ovarian Cancer Cases May Be Treatment-Related Somatic Mutations. J Natl Cancer Inst. 2016;108: pubmed publisher
    Mosaic truncating mutations in the protein phosphatase, Mg(2+)/Mn(2+)-dependent, 1D (PPM1D) gene have recently been reported with a statistically significantly greater frequency in lymphocyte DNA from ovarian cancer case patients ..
  41. Proia D, Nannenga B, Donehower L, Weigel N. Dual roles for the phosphatase PPM1D in regulating progesterone receptor function. J Biol Chem. 2006;281:7089-101 pubmed
    Although protein phosphatase magnesium-dependent 1 delta (PPM1D) was initially characterized as a p53-regulated phosphatase responsible for inactivation of p38 MAPK and consequent inactivation of p53, its overexpression and amplification ..
  42. Chuman Y, Yagi H, Fukuda T, Nomura T, Matsukizono M, Shimohigashi Y, et al. Characterization of the active site and a unique uncompetitive inhibitor of the PPM1-type protein phosphatase PPM1D. Protein Pept Lett. 2008;15:938-48 pubmed
    Protein phosphatase magnesium-dependent 1, delta (PPM1D) is a member of the PPM1 (formerly PP2C) protein phosphatase family, and is induced in response to DNA damage...
  43. Buss M, Read T, Schniederjan M, Gandhi K, Castellino R. HDM2 promotes WIP1-mediated medulloblastoma growth. Neuro Oncol. 2012;14:440-58 pubmed publisher
    Medulloblastoma is the most common malignant childhood brain tumor. The protein phosphatase and oncogene WIP1 is over-expressed or amplified in a significant number of primary human medulloblastomas and cell lines...
  44. Han H, Yu E, Song J, Park J, Jang S, Choi J. The estrogen receptor alpha pathway induces oncogenic Wip1 phosphatase gene expression. Mol Cancer Res. 2009;7:713-23 pubmed publisher
    Wild-type p53-induced phosphatase (Wip1) is a serine/threonine phosphatase induced by DNA-damaging agents...
  45. Bernards R. Wip-ing out cancer. Nat Genet. 2004;36:319-20 pubmed
  46. Wu B, Guo B, Kang J, Deng X, Fan Y, Zhang X, et al. PPM1D exerts its oncogenic properties in human pancreatic cancer through multiple mechanisms. Apoptosis. 2016;21:365-78 pubmed publisher
    Protein phosphatase, Mg(2+)/Mn(2+) dependent, 1D (PPM1D) is emerging as an oncogene by virtue of its negative control on several tumor suppressor pathways...
  47. Zhou X, Groves N, Meier I. SUN anchors pollen WIP-WIT complexes at the vegetative nuclear envelope and is necessary for pollen tube targeting and fertility. J Exp Bot. 2015;66:7299-307 pubmed publisher
    ..The observed pollen defects are similar to phenotypes observed in a wip1-1 wip2-1 wip3-1 wit1-1 wit2-1 mutant...
  48. Peng B, Wang J, Hu Y, Zhao H, Hou W, Zhao H, et al. Modulation of LSD1 phosphorylation by CK2/WIP1 regulates RNF168-dependent 53BP1 recruitment in response to DNA damage. Nucleic Acids Res. 2015;43:5936-47 pubmed publisher
    ..of LSD1 at S131 and S137 was mediated by casein kinase 2 (CK2) and wild-type p53-induced phosphatase 1 (WIP1), respectively. LSD1, RNF168 and 53BP1 interacted with each other directly...
  49. He Z, Hu W, Zhang M, Yang Z, Zhu H, Xing D, et al. Wip1 phosphatase modulates both long-term potentiation and long-term depression through the dephosphorylation of CaMKII. Cell Adh Migr. 2016;10:237-47 pubmed publisher
    ..In this study, we report that Wip1, a protein phosphatase, is essential for long-term potentiation (LTP) and long-term depression (LTD) processes...
  50. An H, Lu X, Liu D, Yarbrough W. LZAP inhibits p38 MAPK (p38) phosphorylation and activity by facilitating p38 association with the wild-type p53 induced phosphatase 1 (WIP1). PLoS ONE. 2011;6:e16427 pubmed publisher
    ..the ability of LZAP to alter p38 phosphorylation depended, at least partially, on the p38 phosphatase, Wip1. Expression of LZAP increased both LZAP and Wip1 binding to p38...
  51. Voss M, Paterson J, Kelsall I, Martin Granados C, Hastie C, Peggie M, et al. Ppm1E is an in cellulo AMP-activated protein kinase phosphatase. Cell Signal. 2011;23:114-24 pubmed publisher
    ..The data indicate that Ppm1E and probably PpM1F are in cellulo AMPK phosphatases and that Ppm1E is a potential anti-diabetic drug target. ..
  52. Sun G, Zhang J, Ma X, Wang Y, Cheng Y, Hu W. Overexpression of Wild-Type p53-Induced Phosphatase 1 Confers Poor Prognosis of Patients with Nasopharyngeal Carcinoma. Pathol Oncol Res. 2015;21:283-91 pubmed publisher
    ..carcinoma and the biological effect in its cell line by siRNA targeting wild-type p53-induced phosphatase 1 (Wip1)...
  53. Zhang Y, Sun H, He G, Liu A, Wang F, Wang L. WIP1 regulates the proliferation and invasion of nasopharyngeal carcinoma in vitro. Tumour Biol. 2014;35:7651-7 pubmed publisher
    Wild-type p53-induced phosphatase (WIP1) is overexpressed and functionally altered in multiple human malignancies. The present study investigated its abnormal expression and dysfunctions in nasopharyngeal carcinoma (NPC) in vitro...
  54. Yang H, Gao X, Li P, Jiang T. PPM1D overexpression predicts poor prognosis in non-small cell lung cancer. Tumour Biol. 2015;36:2179-84 pubmed publisher
    It has been reported that protein phosphatase, Mg(2+)/Mn(2+) dependent, 1D (PPM1D) plays an important role in cancer tumorigenesis...
  55. Coombs C, Zehir A, Devlin S, Kishtagari A, Syed A, Jonsson P, et al. Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes. Cell Stem Cell. 2017;21:374-382.e4 pubmed publisher
    ..CH was associated with increased age, prior radiation therapy, and tobacco use. PPM1D and TP53 mutations were associated with prior exposure to chemotherapy...
  56. Issler M, Mombach J. MicroRNA-16 feedback loop with p53 and Wip1 can regulate cell fate determination between apoptosis and senescence in DNA damage response. PLoS ONE. 2017;12:e0185794 pubmed publisher
    ..levels of damage and contemplates the influence of miR-16 through its positive feedback loop formed with p53 and Wip1. The model reproduces the observed cellular phenotypes in experiments: oscillatory (for low DNA damage) regulated ..
  57. Wen J, Lee J, Malhotra A, Nahta R, Arnold A, Buss M, et al. WIP1 modulates responsiveness to Sonic Hedgehog signaling in neuronal precursor cells and medulloblastoma. Oncogene. 2016;35:5552-5564 pubmed publisher
    High-level amplification of the protein phosphatase PPM1D (WIP1) is present in a subset of medulloblastomas (MBs) that have an expression profile consistent with active Sonic Hedgehog (SHH) signaling...
  58. Tang Y, Pan B, Zhou X, Xiong K, Gao Q, Huang L, et al. Wip1-dependent modulation of macrophage migration and phagocytosis. Redox Biol. 2017;13:665-673 pubmed publisher
    ..Here, we show that Wip1, a member of the PP2C family of Ser/Thr protein phosphatases, modulates macrophage migration and phagocytosis ..
  59. Nomura M, Mukasa A, Nagae G, Yamamoto S, Tatsuno K, Ueda H, et al. Distinct molecular profile of diffuse cerebellar gliomas. Acta Neuropathol. 2017;134:941-956 pubmed publisher
    ..Alterations that cause loss of p53 function including TP53 mutation (n = 9), PPM1D mutation (n = 2), and a novel type of PPM1D fusion (n = 1), were also frequent...
  60. Wang P, Rao J, Yang H, Zhao H, Yang L. Wip1 over-expression correlated with TP53/p14(ARF) pathway disruption in human astrocytomas. J Surg Oncol. 2011;104:679-84 pubmed publisher
    b>Wip1 over-expression inhibits p53 function and reduces selection for TP53 mutations during cancer progression...
  61. Cha H, Lowe J, Li H, Lee J, Belova G, Bulavin D, et al. Wip1 directly dephosphorylates gamma-H2AX and attenuates the DNA damage response. Cancer Res. 2010;70:4112-22 pubmed publisher
    ..Here, we report that the wild-type p53-induced phosphatase 1 (Wip1) phosphatase, which is often overexpressed in a variety of tumors, effectively dephosphorylates gamma-H2AX in vitro ..
  62. Zhu Y, Bulavin D. Wip1-dependent signaling pathways in health and diseases. Prog Mol Biol Transl Sci. 2012;106:307-25 pubmed publisher
    ..highlights the importance of a new member of the PP2C family of phosphatase, Wild-type p53 induced phosphatase 1 (Wip1), in regulating stress-induced and DNA damage-induced networks...
  63. Crescenzi E, Raia Z, Pacifico F, Mellone S, Moscato F, Palumbo G, et al. Down-regulation of wild-type p53-induced phosphatase 1 (Wip1) plays a critical role in regulating several p53-dependent functions in premature senescent tumor cells. J Biol Chem. 2013;288:16212-24 pubmed publisher
    ..We found that expression of wild-type p53-induced phosphatase 1 (Wip1) is markedly down-regulated during persistent DNA damage and after drug release during the acquisition of the ..
  64. Goloudina A, Kochetkova E, Pospelova T, Demidov O. Wip1 phosphatase: between p53 and MAPK kinases pathways. Oncotarget. 2016;7:31563-71 pubmed publisher
    ..Wild type p53-induced phosphatase, Wip1, is involved in governance of both pathways...
  65. Morimoto H, Okamura H, Haneji T. Interaction of protein phosphatase 1 delta with nucleolin in human osteoblastic cells. J Histochem Cytochem. 2002;50:1187-93 pubmed
    ..These results indicate that PP1delta was associated with nucleolin in the nucleolus of MG63 and Saos-2 cells and that nucleolin is a possible candidate substrate for PP1delta. ..
  66. Jeong H, Gil N, Lee H, Cho S, Kim K, Chun K, et al. Timely Degradation of Wip1 Phosphatase by APC/C Activator Protein Cdh1 is Necessary for Normal Mitotic Progression. J Cell Biochem. 2015;116:1602-12 pubmed publisher
    b>Wip1 belongs to the protein phosphatase C (PP2C) family, of which expression is up-regulated by a number of external stresses, and serves as a stress modulator in normal physiological conditions...
  67. Cardoso M, Paulo P, Maia S, Teixeira M. Truncating and missense PPM1D mutations in early-onset and/or familial/hereditary prostate cancer patients. Genes Chromosomes Cancer. 2016;55:954-961 pubmed publisher
    Truncating activating mutations in the last exon of PPM1D have been described in patients with breast, ovarian, colorectal and non-small cell lung cancer, but recent data indicate that they may be associated with previous chemotherapy...
  68. Lin J, Zhang Q, Lu Y, Xue W, Xu Y, Zhu Y, et al. Downregulation of HIPK2 increases resistance of bladder cancer cell to cisplatin by regulating Wip1. PLoS ONE. 2014;9:e98418 pubmed publisher
    ..HIPK2 overexpression partially overcomes cisplatin resistance in RT4-CisR cell. Furthermore, we showed that Wip1 (wild-type p53-induced phosphatase 1) expression is upregulated in RT4-CisR cell compared with RT4 cell, and HIPK2 ..
  69. Filipponi D, Müller J, Emelyanov A, Bulavin D. Wip1 controls global heterochromatin silencing via ATM/BRCA1-dependent DNA methylation. Cancer Cell. 2013;24:528-41 pubmed publisher
    b>Wip1 phosphatase is emerging as an important regulator of tumorigenesis, but no unifying mechanistic network has been proposed...
  70. Hirano K, Ito M, Hartshorne D. Interaction of the ribosomal protein, L5, with protein phosphatase type 1. J Biol Chem. 1995;270:19786-90 pubmed
    ..These data indicate that L5 binds to the catalytic subunit of the type 1 protein phosphatase and may act as a target molecule for phosphatase in ribosomal function or other cell mechanisms. ..
  71. Yin H, Yan Z, Liang Y, Liu B, Su Q. Knockdown of protein phosphatase magnesium-dependent 1 (PPM1D) through lentivirus-mediated RNA silencing inhibits colorectal carcinoma cell proliferation. Technol Cancer Res Treat. 2013;12:537-43 pubmed publisher
    Colorectal cancer is one of the most common cancers in the world. Protein phosphatase magnesium-dependent 1 d (PPM1D) is aberrantly upregulated in many human carcinoma cells, and recent research has suggested that it could be a potential ..
  72. Cha B, Lee J, Kim S, Cha H, Lee S. The modulation of the oxidative stress response in chondrocytes by Wip1 and its effect on senescence and dedifferentiation during in vitro expansion. Biomaterials. 2013;34:2380-8 pubmed publisher
    ..As demonstrated in the current study, wild-type p53-inducible phosphatase (Wip1), a well-established stress modulator, was highly expressed in early-passage chondrocytes, but declined rapidly ..
  73. Tatewaki N, Konishi T, Nakajima Y, Nishida M, Saito M, Eitsuka T, et al. Squalene Inhibits ATM-Dependent Signaling in γIR-Induced DNA Damage Response through Induction of Wip1 Phosphatase. PLoS ONE. 2016;11:e0147570 pubmed publisher
    ..A recent study reported that Wip1, a protein phosphatase, de-phosphorylates serine 1981 of ATM during the DNA damage response...
  74. Yang S, Dong S, Qu X, Zhong X, Zhang Q. Clinical significance of Wip1 overexpression and its association with the p38MAPK/p53/p16 pathway in NSCLC. Mol Med Rep. 2017;15:719-723 pubmed publisher
    b>Wip1 is deregulated in numerous human malignancies. However, its roles in non?small cell lung cancer (NSCLC) remain unclear. In the current study, the expression of Wip1 was investigated in NSCLC and its clinical significance was detected...