Property Summary

NCBI Gene PubMed Count 98
PubMed Score 162.21
PubTator Score 127.67

Knowledge Summary


No data available



  Differential Expression (7)

Disease log2 FC p
osteosarcoma -3.033 4.5e-12
group 3 medulloblastoma 2.100 3.3e-03
lung cancer -1.600 1.9e-03
subependymal giant cell astrocytoma -2.105 1.3e-02
invasive ductal carcinoma -1.360 7.8e-04
spina bifida -1.387 4.7e-02
ovarian cancer -1.700 2.9e-04

Gene RIF (88)

26847329 Chemotherapy exposure and age influence the accumulation of PPM1D mutations in the peripheral blood mononuclear cells of ovarian cancer patients.
26824362 squalene inhibits the ATM-dependent signaling pathway following DNA damage through intracellular induction of Wip1 expression.
26714478 PPM1D suppresses pancreatic cancer cell apoptosis via inhibition of the p38 MAPK/p53 pathway through both dephosphorylation of p38 MAPK and downregulation of ASPP2.
26351212 Knockdown of Wip1 enhances sensitivity to radiation in HeLa cells by inhibiting cell proliferation and inducing apoptosis through activation of p38 MAPK.
26006237 p21 might contribute to positive regulation of WIP1, resulting in dephosphorylation of the histone H2A variant gammaH2AX.
25879755 Study reveals a mechanism of stem cell aging, in which distinct effects of p53 and mTORC1 pathways on HSC aging are governed by Wip1.
25797250 WIP1 silencing reduced expression of MMP-9, VEGF-C, cyclin D1, and c-Myc, as well as migration and invasion of salivary adenoid cystic carcinoma cells. WIP1 expression was positively associated with ACC metastasis and prognosis.
25742468 The truncating mutations of PPM1D are present in blood DNA of NSCLC patients.
25659035 ATM kinase and Wip1 phosphatase were identified as opposing regulators of DAXX-S564 phosphorylation and the role of DAXX phosphorylation and DAXX itself are independent of p53-mediated gene expression.
25658463 data suggests that WIP1 inhibition represents a novel therapeutic approach to neuroblastoma that could be integrated with current chemotherapeutic approaches
25649870 Results showed evidence that Wip1 underwent Cdh1-dependent proteolysis during mitosis and sustained Wip1 activity during mitosis, resulting in mitotic delay at the metaphase to anaphase transition.
25412952 PPM1D plays an important role in the progression of NSCLC.
25154814 PPM1D plays an important role in promoting CDDP resistance.
25123458 High PPM1D expression is associated with lung cancer.
25060857 Wip1 may be involved in the biological processes of nasopharyngeal cancer cell proliferation, apoptosis, and migration and invasion.
24970693 Wip1 protein was increased in kidney carcinoma.
24922655 High PPM1D expression is associated with prostate cancer.
24880341 Gain-of-function PPM1D mutations are associated with brainstem gliomas.
24846322 Results show that downregulation of HIPK2 increases resistance of bladder cancer cell to cisplatin by regulating Wip1.
24801909 WIP1 knockdown inhibited the invasiveness of CNE-2 and 5-8F cells and was associated with the down-regulation of the expression of matrix metallopeptidase 9
24711418 PP4 and Wip1 are differentially required to counteract the p53-dependent cell cycle arrest in G1 and G2, by antagonizing early or late p53-mediated responses, respectively
24632620 Results demonstrate increased WIP1 expression in metastatic medulloblastomas, and inferior survival in patients with WIP1 high-expressing medulloblastoma.
24395919 Expression of Wip1 in neutrophils was downregulated quickly after neutrophil activation through JNK-microRNA-16 pathway. It was negatively correlated with inflammatory cytokine productions of neutrophils in sepsis patients.
24272082 Wip1 may be involved in the biological processes of non small cell lung cancer cell proliferation, cell apoptosis, and cell cycle.
24262437 PPM1D mutations in the mosaic state predispose women to breast and ovarian cancer in the absence of a family history of cancer
24135283 Wip1 plays an important role in the regulation of global heterochromatin silencing and thus is critical in maintaining genome integrity
23907458 BAX dephosphorylation of Wip1 phosphatase is an important regulator of resistance to anticancer therapy.
23907125 Genetic variants and mutations of PPM1D control the response to DNA damage.
23906386 phosphatase activity toward phosphopeptide substrates by PP2Calpha and Wip1 requires the binding of a Mg(2)+ ion to the low-affinity site.
23871434 In response to ionizing radiation, HIPK2 phosphorylation promotes inhibition of WIP1 phosphorylation through dissociation of WIP1 from HIPK2, followed by stabilization of WIP1 for termination of the ATM-mediated double-strand break signaling cascade.
23745790 PPM1D plays a crucial role in colorectal carcinoma cell proliferation and colony formation.
23679302 High WIP1 expression is associated with colorectal cancer.
23649806 PPM1D/Wip1 mutations in tumor cells impair the p53-dependent G1 checkpoint in the DNA Damage Response pathway
23612976 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.
23556002 PPM1D mRNA overexpression correlated with poor prognosis in patients with hepatocellular carcinoma.
23306038 Stable expression of Wip1 gene in chondrocytes attenuated the onset of senescence and dedifferentiation during in vitro expansion, resulting in the retention of a chondrocyte phenotype during prolonged culture.
23255129 Downregulation of Wip1 phosphatase modulates the cellular threshold of DNA damage signaling in mitosis.
23242139 rare protein-truncating variants in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer
23146903 data uncover a role for WIP1 in modulating the activity of GLI1 and in sustaining cancer cell growth and cancer stem cell self-renewal induced by activation of the HH pathway
22379189 Combined WIP1 and HDM2 inhibition is more effective than WIP1 inhibition alone in blocking growth of WIP1 high-expressing medulloblastoma cells.
22340722 Wip1 plays a role in regulating stress-induced & DNA-damage-induced networks, tumorigenesis, neurogenesis and aging. Review.
22325093 The results of this study suggested that Wip1 may be related to pathological diagnosis and prognosis evaluation for malignant gliomas.
22201816 Wip1 functions to abrogate cell cycle checkpoints and inhibit senescence, apoptosis, DNA repair, and the production of inflammatory cytokines
22115592 SPI-001 is a small molecule inhibitor of p53-inducible protein phosphatase PPM1D
21927021 Our findings establish for the first time that PPM1D confers CDDP resistance in OVCA cells through attenuating CDDP-induced, Chk1-mediated, p53-dependent apoptosis
21734451 Wip1 provides ample time for cells to be ready for mitosis, which is at least mediated through increased inhibitory phospho-tyrosine level on CDC2.
21695702 Wip1 over-expression correlated with TP53/p14(ARF) pathway disruption in human astrocytomas.
21336731 Down-regulation of PPM1D resulted in significantly increased cell apoptosis and reduced cell proliferation and invasion potential in U87-MG cells.
21283629 the ability of LZAP to alter p38 phosphorylation depended, at least partially, on the p38 phosphatase, Wip1
21281403 the increased expression of Wip1 in cancer epithelial cells has significant value for tumor progression and the clinical prognosis of patients with primary lung adenocarcinoma
20668064 results suggest an important role of miR-16 in the regulation of Wip1 phosphatase in the DNA damage response and mammary tumorigenesis.
20543821 PPM1D is consistently overexpressed when amplified in breast cancer; however, PPM1D overexpression is more pervasive than gene amplification.
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20367961 The high expression of Wip1 mRNA and its protein in breast cancer tissue may promote the growth of breast cancer.
20118229 Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-H2AX and suppresses DNA double strand break repair.
20101220 Wip1 has an essential role in dephosphorylation of gamma-H2AX to silence the checkpoint and restore chromatin structure once DNA damage is repaired.
20093361 Wip1 (wild-type p53-induced phosphatase) expression is temporally induced by c-Jun and p53 in response to UV irradiation
20007970 Nuclear factor-kappaB (NF-kappaB) is a novel positive transcriptional regulator of the oncogenic Wip1 phosphatase
19713933 Findings uncover Wip1 as a first in class recovery competence gene, and suggest that the principal function of Wip1 in cellular transformation is to retain proliferative capacity in the face of oncogene-induced stress.
19435816 Results indicate that Wip1 up-regulation is important in the pathogenesis of p53(+) and ER(+) breast cancer through the inactivation of p53 by dephosphorylation and the amplification of subsequent estrogenic effects through the E(2)-ERalpha-Wip1 pathway.
19377466 WIP1 is a direct phosphatase of Ser 536 of the p65 subunit of NF-kappaB and negatively regulates NF-kappaB signalling.
19015127 Characterization of a conserved p53 response element located in the 5' untranslated region of the PPM1D gene that is required for the p53-dependent induction of transcription from the human PPM1D promoter.
18991770 identification of the active center and further elucidation of the substrate preference of PPM1D; findings showed that the putative active site residues of PPM1D are highly conserved among the PPM1 family members
18845566 PPM1D430, a novel alternative splicing variant of the human PPM1D, can dephosphorylate p53 and exhibits specific tissue expression
18482988 ATO-induced activation of Chk2/p53 and p38 MAPK/p53 apoptotic pathways can be enhanced by siRNA-mediated suppression of Wip1 expression, further indicating that ATO inhibits Wip1 phosphatase in vivo
18328948 Our findings demonstrate that PPM1D is involved in the regulation of cell proliferation in breast cancer in a p53-dependent manner and that overexpression of PPM1D contributes to malignant phenotype by promoting sustained cell growth and cell survival.
17977650 PPM1D contributes to breast cancer associated phenotypic characteristics by directly or indirectly affecting several important cellular signaling pathways.
17939684 The Wip1 phosphatase PPM1D dephosphorylates SQ/TQ motifs in checkpoint substrates phosphorylated by PI3K-like kinases.
17936559 Wip1 acts as a gatekeeper in the Mdm2-p53 regulatory loop by stabilizing Mdm2 and promoting Mdm2-mediated proteolysis of p53.
17685927 WIP1 is expressed in non-neoplastic gastric mucosa and is frequently overexpressed in gastric cancers.
17016428 Operates within the map kinase kinase 6/p38 map kinase signaling pathway to promote ErbB2-driven mammary gland tumorigenesis in transgenic mice.
16949371 Wip1 phosphatase is an integral component of an ATM-dependent signaling pathway.
16936775 These results indicate that Wip1 is one of the phosphatases regulating the activity of Chk2 in response to DNA damage.
16912047 E2F and Wip1 are modulators of E2F1-induced apoptosis involving p38 MAP kinase
16897432 Wip1 overexpression abrogates the homeostatic balance maintained through the p38-p53-Wip1 pathway, and contributes to malignant progression by inactivating wild-type p53 and p38 MAPK as well as decreasing p16 protein levels in human breast tissues.
16798742 an intrinsic kinase activity of Chk2, but not phosphatase activity of Wip1, is required for the association of fulllength Chk2 and Wip1
16352595 PPM1D promotes breast tumor growth both by inhibiting p53 activity and by enhancing steroid hormone receptor action
16352595 Demonstrated the ability of protein phosphatase 1D magnesium-dependent, delta isoform (PPM1D) to positively modulate the activity of type I and II nuclear receptors.
16314645 Increased protein-levels of PPM1D may link the TP53 and RB1 tumor suppressor pathways to medulloblastoma pathomechanisms.
16311512 Wip1 acts as a negative regulator of Chk2 and inhibition of Wip1 expression by RNA interference results in abnormally sustained Thr68 phosphorylation of Chk2.
16254685 PPM1D is frequently activated through amplification in aggressive primary breast tumours
15870257 Primary function of PPM1D is to reverse the p53 and Chk1-induced DNA damage and cell cycle checkpoint responses and return the cell to a homeostatic state following completion of DNA repair.
15807522 suggest that substrate recognition by Wip1 is centered toward a very narrow region around the pTXpY sequence
15327777 Data demonstrate that p53-induced phosphatase PPM1D interacts with the nuclear isoform of uracil DNA glycosylase, UNG2, and suppresses base excision repair.
15054481 ablation of gene confers resistance to breast tumors induced by certain oncogenes
12021785 PPM1D amplification contributes to the development of human cancers by suppressing p53 activation
12021784 PPM1D, encoding a serine/threonine protein phosphatase, lies within an epicenter of the region at 17q23, is amplified in breast cancer
11809801 Functional study of the mouse homolog

AA Sequence


Text Mined References (101)

PMID Year Title
26871637 2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
26847329 2016 Somatic Mosaic Mutations in PPM1D and TP53 in the Blood of Women With Ovarian Carcinoma.
26824362 2016 Squalene Inhibits ATM-Dependent Signaling in ?IR-Induced DNA Damage Response through Induction of Wip1 Phosphatase.
26714478 2016 PPM1D exerts its oncogenic properties in human pancreatic cancer through multiple mechanisms.
26351212 2014 Knockdown of Wip1 Enhances Sensitivity to Radiation in HeLa Cells Through Activation of p38 MAPK.
26006237 2015 Spontaneous ?H2AX Foci in Human Solid Tumor-Derived Cell Lines in Relation to p21WAF1 and WIP1 Expression.
25879755 2015 Wip1 deficiency impairs haematopoietic stem cell function via p53 and mTORC1 pathways.
25797250 2015 WIP1 stimulates migration and invasion of salivary adenoid cystic carcinoma by inducing MMP-9 and VEGF-C.
25742468 2015 Truncating mutations of PPM1D are found in blood DNA samples of lung cancer patients.
25659035 2015 DNA damage-induced regulatory interplay between DAXX, p53, ATM kinase and Wip1 phosphatase.
25658463 2015 WIP1 phosphatase as a potential therapeutic target in neuroblastoma.
25649870 2015 Timely Degradation of Wip1 Phosphatase by APC/C Activator Protein Cdh1 is Necessary for Normal Mitotic Progression.
25412952 2015 PPM1D overexpression predicts poor prognosis in non-small cell lung cancer.
25154814 2015 Akt confers cisplatin chemoresistance in human gynecological carcinoma cells by modulating PPM1D stability.
25123458 2014 PPM1D silencing by RNA interference inhibits the proliferation of lung cancer cells.
25060857 2015 Overexpression of Wild-Type p53-Induced Phosphatase 1 Confers Poor Prognosis of Patients with Nasopharyngeal Carcinoma.
24970693 2015 Expression of Wip1 in kidney carcinoma and its correlation with tumor metastasis and clinical significance.
24922655 2014 PPM1D as a novel biomarker for prostate cancer after radical prostatectomy.
24880341 2014 Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas.
24846322 2014 Downregulation of HIPK2 increases resistance of bladder cancer cell to cisplatin by regulating Wip1.
24801909 2014 WIP1 regulates the proliferation and invasion of nasopharyngeal carcinoma in vitro.
24711418 2014 Distinct phosphatases antagonize the p53 response in different phases of the cell cycle.
24632620 2015 The WIP1 oncogene promotes progression and invasion of aggressive medulloblastoma variants.
24395919 2014 Phosphatase Wip1 negatively regulates neutrophil migration and inflammation.
24272082 2014 Proto-oncogene Wip1, a member of a new family of proliferative genes in NSCLC and its clinical significance.
24262437 2014 PPM1D mutations in circulating white blood cells and the risk for ovarian cancer.
24135283 2013 Wip1 controls global heterochromatin silencing via ATM/BRCA1-dependent DNA methylation.
23907458 2013 Wip1 suppresses apoptotic cell death through direct dephosphorylation of BAX in response to ?-radiation.
23907125 2013 Genetic variants and mutations of PPM1D control the response to DNA damage.
23906386 2013 Binding of a third metal ion by the human phosphatases PP2C? and Wip1 is required for phosphatase activity.
23871434 2013 WIP1, a homeostatic regulator of the DNA damage response, is targeted by HIPK2 for phosphorylation and degradation.
23745790 2013 Knockdown of protein phosphatase magnesium-dependent 1 (PPM1D) through lentivirus-mediated RNA silencing inhibits colorectal carcinoma cell proliferation.
23679302 2013 Expression and significance of the Wip1 proto-oncogene in colorectal cancer.
23649806 2013 Gain-of-function mutations of PPM1D/Wip1 impair the p53-dependent G1 checkpoint.
23612976 2013 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.
23556002 2013 Protein phosphatase magnesium-dependent 1? (PPM1D) mRNA expression is a prognosis marker for hepatocellular carcinoma.
23306038 2013 The modulation of the oxidative stress response in chondrocytes by Wip1 and its effect on senescence and dedifferentiation during in vitro expansion.
23255129 2013 Downregulation of Wip1 phosphatase modulates the cellular threshold of DNA damage signaling in mitosis.
23242139 2013 Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23146903 2013 WIP1 phosphatase modulates the Hedgehog signaling by enhancing GLI1 function.
22379189 2012 HDM2 promotes WIP1-mediated medulloblastoma growth.
22340722 2012 Wip1-dependent signaling pathways in health and diseases.
22325093 2012 Over-expression of wild-type p53-induced phosphatase 1 confers poor prognosis of patients with gliomas.
22201816 2012 Regulation of the Wip1 phosphatase and its effects on the stress response.
22115592 2012 A small molecule inhibitor of p53-inducible protein phosphatase PPM1D.
21927021 2012 The oncogenic phosphatase PPM1D confers cisplatin resistance in ovarian carcinoma cells by attenuating checkpoint kinase 1 and p53 activation.
21734451 2011 Wip1 contributes to cell homeostasis maintained by the steady-state level of Wtp53.
21695702 2011 Wip1 over-expression correlated with TP53/p14(ARF) pathway disruption in human astrocytomas.
21336731 2011 PPM1D silencing by lentiviral-mediated RNA interference inhibits proliferation and invasion of human glioma cells.
21283629 2011 LZAP inhibits p38 MAPK (p38) phosphorylation and activity by facilitating p38 association with the wild-type p53 induced phosphatase 1 (WIP1).
21281403 2011 Oncogenic phosphatase Wip1 is a novel prognostic marker for lung adenocarcinoma patient survival.
20801214 2011 Ppm1E is an in cellulo AMP-activated protein kinase phosphatase.
20668064 2010 Oncogenic Wip1 phosphatase is inhibited by miR-16 in the DNA damage signaling pathway.
20543821 2010 PPM1D gene amplification and overexpression in breast cancer: a qRT-PCR and chromogenic in situ hybridization study.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20367961 2010 [Expression of proto-oncogene Wip1 in breast cancer and its clinical significance].
20118229 2010 Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-H2AX and suppresses DNA double strand break repair.
20101220 2010 Wip1 phosphatase is associated with chromatin and dephosphorylates gammaH2AX to promote checkpoint inhibition.
20093361 2010 Expression of a homeostatic regulator, Wip1 (wild-type p53-induced phosphatase), is temporally induced by c-Jun and p53 in response to UV irradiation.
20007970 2010 Nuclear factor-kappaB (NF-kappaB) is a novel positive transcriptional regulator of the oncogenic Wip1 phosphatase.
19713933 2009 Wip1 confers G2 checkpoint recovery competence by counteracting p53-dependent transcriptional repression.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19435816 2009 The estrogen receptor alpha pathway induces oncogenic Wip1 phosphatase gene expression.
19377466 2009 WIP1 phosphatase is a negative regulator of NF-kappaB signalling.
19015127 2008 Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites.
18991770 2008 Characterization of the active site and a unique uncompetitive inhibitor of the PPM1-type protein phosphatase PPM1D.
18845566 2009 PPM1D430, a novel alternative splicing variant of the human PPM1D, can dephosphorylate p53 and exhibits specific tissue expression.
18482988 2008 Arsenic trioxide augments Chk2/p53-mediated apoptosis by inhibiting oncogenic Wip1 phosphatase.
18328948 2008 PPM1D silencing by RNA interference inhibits proliferation and induces apoptosis in breast cancer cell lines with wild-type p53.
17977650 2008 Identification of differentially expressed genes after PPM1D silencing in breast cancer.
17939684 2007 The Wip1 phosphatase PPM1D dephosphorylates SQ/TQ motifs in checkpoint substrates phosphorylated by PI3K-like kinases.
17936559 2007 The Wip1 Phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop.
17685927 2007 Increased wild-type p53-induced phosphatase 1 (Wip1 or PPM1D) expression correlated with downregulation of checkpoint kinase 2 in human gastric carcinoma.
17016428 2007 The role of the MKK6/p38 MAPK pathway in Wip1-dependent regulation of ErbB2-driven mammary gland tumorigenesis.
16949371 2006 Wip1 phosphatase modulates ATM-dependent signaling pathways.
16936775 2007 The Wip1 phosphatase (PPM1D) antagonizes activation of the Chk2 tumour suppressor kinase.
16912047 2006 E2F1 modulates p38 MAPK phosphorylation via transcriptional regulation of ASK1 and Wip1.
16897432 2007 Overexpression of the wip1 gene abrogates the p38 MAPK/p53/Wip1 pathway and silences p16 expression in human breast cancers.
16798742 2006 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.
16625196 2006 DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.
16352595 2006 Dual roles for the phosphatase PPM1D in regulating progesterone receptor function.
16314645 2005 Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma.
16311512 2006 Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase.
16254685 2006 The serine-threonine protein phosphatase PPM1D is frequently activated through amplification in aggressive primary breast tumours.
15870257 2005 PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints.
15807522 2005 Substrate specificity of the human protein phosphatase 2Cdelta, Wip1.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15327777 2004 The p53-induced oncogenic phosphatase PPM1D interacts with uracil DNA glycosylase and suppresses base excision repair.
15054481 2004 Wip-ing out cancer.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12878157 2003 Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12185196 2002 Interaction of protein phosphatase 1 delta with nucleolin in human osteoblastic cells.
12021784 2002 Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23.
11809801 2002 Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control.
11101529 2000 Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry.
11101524 2000 p53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation.
9177166 1997 Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner.
7649987 1995 Interaction of the ribosomal protein, L5, with protein phosphatase type 1.
7566098 1995 Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence.