Phosphatase Subfamily PPM1D
From PhosphataseWiki
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].
References
- Buss MC, Remke M, Lee J, Gandhi K, Schniederjan MJ, Kool M, Northcott PA, Pfister SM, Taylor MD, and Castellino RC. The WIP1 oncogene promotes progression and invasion of aggressive medulloblastoma variants. Oncogene. 2015 Feb 26;34(9):1126-40. DOI:10.1038/onc.2014.37 |
- Chen Z, Yi W, Morita Y, Wang H, Cong Y, Liu JP, Xiao Z, Rudolph KL, Cheng T, and Ju Z. Wip1 deficiency impairs haematopoietic stem cell function via p53 and mTORC1 pathways. Nat Commun. 2015 Apr 16;6:6808. DOI:10.1038/ncomms7808 |
