Phosphatase Subfamily PPM1D

Phosphatase Classification: Fold PPM (PP2C): Superfamily PPM (PP2C): Family PPM (PP2C): Subfamily PPM1D (WIP1)

Evolution

PPM1D (WIP1) most likely emerged in holozoa. It is single copy in most genomes, including human genome. See internal gOrtholog database.

Domain

PPM1D (WIP1) has a single structure domain, the phosphatase domain of PPM (PP2C) fold.

Function

PPM1D is also known as WIP1 (Wild-type p53-induced phosphatase 1). It 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. It is therefore involved in diverse pathways. Below are some examples of its functions:

• PPM1D (WIP1) oncogene promotes progression and invasion of aggressive medulloblastoma variants [1].

• PPM1D (WIP1) is highly expressed in HSCs but decreases with age, and WIP1-deficient (Wip1-/-) mice exhibited multifaceted HSC aging phenotypes, including the increased pool size and impaired repopulating activity [2].

• PPM1D (WIP1) controls antigen-independent B cell development in a p53-dependent manner [3].

PPM1D may serve as a biomarker. The truncating mutations at exon 6 of PPM1D were found in blood DNA of non-small-cell lung cancer patients (NSCLC) [4].

References

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