PPM1D

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. [provided by RefSeq]

protein phosphatase 1D magnesium-dependent, delta isoform

Involved in the negative regulation of p53 expression (PubMed:23242139).
Required for the relief of p53-dependent checkpoint mediated cell cycle arrest. Binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1 which contributes to the functional inactivation of these proteins (PubMed:15870257, PubMed:16311512).
Mediates MAPK14 dephosphorylation and inactivation (PubMed:21283629).
Is also an important regulator of global heterochromatin silencing and critical in maintaining genome integrity (By similarity).

Cellular response to starvationIEA:Ensembl
DNA damage response, signal transduction by p53 class mediatorIEA:Ensembl
DNA methylationISS:UniProtKB
G2/M transition of mitotic cell cycleIEA:Ensembl
Heterochromatin assemblyISS:UniProtKB
Negative regulation of cell population proliferationManual Assertion Based On ExperimentTAS:ProtInc
Negative regulation of gene expression, epigeneticManual Assertion Based On ExperimentIMP:UniProtKB
Peptidyl-threonine dephosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein dephosphorylationManual Assertion Based On ExperimentTAS:ProtInc
Regulation of transcription initiation from RNA polymerase II promoterTAS:Reactome
Response to bacteriumIEA:Ensembl
Response to radiationManual Assertion Based On ExperimentTAS:ProtInc

Nucleus
Cytoplasm, cytosol

Jansen-de Vries syndrome (JDVS):
An autosomal dominant neurodevelopmental disorder characterized by mild to severe intellectual disability, psychomotor developmental delay, speech delay, and behavioral manifestations including attention deficit-hyperactivity disorder, autism and anxiety disorders. Most patients have variable additional features, including feeding and gastrointestinal difficulties, high pain threshold, hypersensitivity to sound, hypotonia, broad-based gait, and dysmorphic features, including mild facial abnormalities, strabismus, and small hands and feet.
Breast cancer (BC):
A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.
Ovarian cancer (OC):
The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.