HCSGD entry for PPM1D
1. General information
| Official gene symbol | PPM1D |
|---|---|
| Entrez ID | 8493 |
| Gene full name | protein phosphatase, Mg2+/Mn2+ dependent, 1D |
| Other gene symbols | PP2C-DELTA WIP1 |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0000086 | G2/M transition of mitotic cell cycle | IEA | biological_process |
| GO:0003824 | Catalytic activity | IEA | molecular_function |
| GO:0004722 | Protein serine/threonine phosphatase activity | IDA IEA | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005634 | Nucleus | TAS | cellular_component |
| GO:0006470 | Protein dephosphorylation | IEA TAS | biological_process |
| GO:0008285 | Negative regulation of cell proliferation | TAS | biological_process |
| GO:0009314 | Response to radiation | TAS | biological_process |
| GO:0009617 | Response to bacterium | IEA | biological_process |
| GO:0035970 | Peptidyl-threonine dephosphorylation | IDA | biological_process |
| GO:0046872 | Metal ion binding | IEA | molecular_function |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.0283540557 | 0.8995670795 | 0.3914350813 | 1.0000000000 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Up | 0.2660255772 |
| GSE13712_SHEAR | Up | 0.1847416613 |
| GSE13712_STATIC | Up | 0.3743781082 |
| GSE19018 | Up | 0.1132433789 |
| GSE19899_A1 | Up | 0.2926914689 |
| GSE19899_A2 | Up | 0.2380112267 |
| PubMed_21979375_A1 | Up | 0.6472371923 |
| PubMed_21979375_A2 | Up | 0.4937460177 |
| GSE35957 | Down | -0.2904708772 |
| GSE36640 | Up | 0.4782665064 |
| GSE54402 | Down | -0.3605307894 |
| GSE9593 | Down | -0.2381883388 |
| GSE43922 | Up | 0.3210876515 |
| GSE24585 | Up | 1.0821719582 |
| GSE37065 | Up | 0.1883141806 |
| GSE28863_A1 | Up | 0.0987991647 |
| GSE28863_A2 | Down | -0.0013761519 |
| GSE28863_A3 | Down | -0.6549916570 |
| GSE28863_A4 | Up | 0.1065432186 |
| GSE48662 | Up | 0.1812107857 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
Not regulated by compounds
- Drugs
Not regulated by drugs
- MicroRNAs
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-29a-3p | MIMAT0000086 | MIRT004044 | Luciferase reporter assay//Microarray//qRT-PCR//Western blot | Functional MTI | 21175813 |
| hsa-miR-16-5p | MIMAT0000069 | MIRT005360 | Northern blot//qRT-PCR//Western blot//Immunoblot//Luciferase reporter assay | Functional MTI | 20668064 |
| hsa-miR-153-3p | MIMAT0000439 | MIRT005682 | Immunoblot//Luciferase reporter assay | Functional MTI (WeaK) | 20668064 |
| hsa-miR-145-5p | MIMAT0000437 | MIRT005683 | Immunoblot//Luciferase reporter assay | Non-Functional MTI | 20668064 |
| hsa-miR-203a | MIMAT0000264 | MIRT005684 | Immunoblot//Luciferase reporter assay | Non-Functional MTI | 20668064 |
| hsa-miR-217 | MIMAT0000274 | MIRT005685 | Immunoblot//Luciferase reporter assay | Functional MTI (WeaK) | 20668064 |
| hsa-miR-26b-5p | MIMAT0000083 | MIRT028938 | Microarray | Functional MTI (Weak) | 19088304 |
| hsa-miR-29c-3p | MIMAT0000681 | MIRT044244 | CLASH | Functional MTI (Weak) | 23622248 |
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- mirRecord
No target information from mirRecord
6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 7 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 27183917 | Cooperation of Nutlin-3a and a Wip1 inhibitor to induce p53 activity |
| 27183917 | To overcome these limitations, we inhibited Mdm2 and simultaneously a second negative regulator of p53, the phosphatase Wip1/PPM1D |
| 27183917 | When combining Nutlin-3a with the Wip1 inhibitor GSK2830371 in the treatment of p53-proficient but not p53-deficient cells, we observed enhanced phosphorylation (Ser 15) and acetylation (Lys 382) of p53, increased expression of p53 target gene products, and synergistic inhibition of cell proliferation |
| 27183917 | Taken together, the inhibition of Wip1 might fortify p53-mediated tumor suppression by Mdm2 antagonists |
| 25879755 | Wip1 deficiency impairs haematopoietic stem cell function via p53 and mTORC1 pathways |
| 25879755 | Wild-type p53-induced phosphatase 1 (Wip1) negatively regulates several tumour suppressor and DNA damage response pathways |
| 25879755 | However, the impact of Wip1 on haematopoietic stem cell (HSC) homeostasis and aging remains unknown |
| 25879755 | Here we show that Wip1 is highly expressed in HSCs but decreases with age |
| 25879755 | Wip1-deficient (Wip1(-/-)) mice exhibited multifaceted HSC aging phenotypes, including the increased pool size and impaired repopulating activity |
| 25879755 | Deletion of p53 rescued the multilineage repopulation defect of Wip1(-/-) HSCs without affecting cellular senescence or apoptosis, indicating that the Wip1-p53 axis regulates HSC differentiation in a manner independent of conventional p53 pathways |
| 25879755 | However, p53 deletion did not influence the increased HSC pool size in Wip1(-/-) mice |
| 25879755 | Interestingly, the expansion of HSCs in Wip1(-/-) mice was due to an mTORC1-mediated HSC proliferation |
| 25879755 | Thus, our study reveals a mechanism of stem cell aging, in which distinct effects of p53 and mTORC1 pathways on HSC aging are governed by Wip1 |
| 24552809 | Wip1 (protein phosphatase Mg(2+)/Mn(2+)-dependent 1D, Ppm1d) is a nuclear serine/threonine protein phosphatase that is induced by p53 following the activation of DNA damage response (DDR) signaling |
| 24552809 | Ppm1d(-/-) mouse embryonic fibroblasts (MEFs) exhibit premature senescence under conventional culture conditions; however, little is known regarding the role of Wip1 in regulating cellular senescence |
| 24552809 | In this study, we found that even at a representative physiological concentration of 3% O2, Ppm1d(-/-) MEFs underwent premature cellular senescence that depended on the functional activation of p53 |
| 24552809 | Interestingly, Ppm1d(-/-) MEFs showed increased H2AX phosphorylation levels without increased levels of reactive oxygen species (ROS) or DNA base damage compared with wild-type (Wt) MEFs, suggesting a decreased threshold for DDR activation or sustained DDR activation during recovery |
| 24552809 | Notably, the increased H2AX phosphorylation levels observed in Ppm1d(-/-) MEFs were primarily associated with S-phase cells and predominantly dependent on the activation of ATM |
| 24552809 | Moreover, these same phenotypes were observed when Wt and Ppm1d(-/-) MEFs were either transiently or chronically exposed to low levels of agents that induce replication-mediated double-stranded breaks |
| 24552809 | These findings suggest that Wip1 prevents the induction of cellular senescence at physiological oxygen levels by attenuating DDR signaling in response to endogenous double-stranded breaks that form during DNA replication |
| 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 |
| 23612976 | 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 senescent phenotype in carcinoma cells |
| 23612976 | We demonstrate that down-regulation of Wip1 is required for maintenance of permanent G2 arrest |
| 23612976 | In fact, we show that forced expression of Wip1 in premature senescent tumor cells induces inappropriate re-initiation of mitosis, uncontrolled polyploid progression, and cell death by mitotic failure |
| 23612976 | Most of the effects of Wip1 may be attributed to its ability to dephosphorylate p53 at Ser(15) and to inhibit DNA damage response |
| 23612976 | On the whole, our data indicate that down-regulation of Wip1 expression during premature senescence plays a pivotal role in regulating several p53-dependent aspects of the senescent phenotype |
| 23514618 | Gene array qPCR analysis of MIA PaCa-2 cells treated with the lead compound revealed significant dose-dependent modulation of a distinct subset of genes, including strong induction of DNA damage responsive genes CDKN1A, DDIT3, GADD45A/G, and PPM1D, and repression of genes involved in telomere maintenance, including hPOT1 and PARP1 |
| 20940041 | Control of p53 and NF-kappaB signaling by WIP1 and MIF: role in cellular senescence and organismal aging |
| 20940041 | WIP1 (wildtype p53-induced phosphatase 1) and MIF (macrophage migration inhibitory factor) are signaling molecules which link together the p53 and NF-kappaB pathways via positive and negative feedback loops |
| 20940041 | Several observations indicate that the activity of WIP1 decreases during the aging process, this being probably attributable to the decline in p53 function |
| 20940041 | Decreased WIP1 activity potentiates the activity of p38MAPK and NF-kappaB signaling leading to premature cellular senescence as well as low-level chronic inflammation |
| 20940041 | We will review the findings linking WIP1 and MIF to specific signaling responses of p53 and NF-kappaB and discuss their role in the regulation of cellular senescence and organismal aging |
| 17432596 | Investigation was performed on the E1A + cHa-ras transformants selected from mice embryonic fibroblasts null at the p38alpha kinase gene or null fibroblasts at the PPM1D gene, which encoded phosphatase Wip1 |
| 17432596 | Absence of Wip1 led to constitutive activation of p38alpha kinase |
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