PPM1D

Description

The PPM1D (protein phosphatase, Mg2+/Mn2+ dependent 1D) is a protein-coding gene located on chromosome 17.

PPM1D (Protein phosphatase 1D) is an enzyme encoded by the PPM1D gene in humans. It belongs to the PP2C family of Ser/Thr protein phosphatases, known to negatively regulate cell stress response pathways. PPM1D expression is induced by TP53/p53 in response to various environmental stresses. While induced by TP53/p53, PPM1D negatively regulates p38 MAP kinase activity, reducing p53 phosphorylation and suppressing p53-mediated transcription and apoptosis. This feedback regulation of p38-p53 signaling contributes to growth inhibition and suppression of stress-induced apoptosis. The gene is located in a region often amplified in breast cancer, suggesting a role in cancer development.

PPM1D is involved in the negative regulation of p53 expression, required for the relief of p53-dependent checkpoint mediated cell cycle arrest. It binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1, contributing to their functional inactivation. PPM1D mediates MAPK14 dephosphorylation and inactivation. It is also a key regulator of global heterochromatin silencing and crucial for maintaining genome integrity.

PPM1D is also known as IDDGIP, JDVS, PP2C-DELTA, WIP1.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing