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
- 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 |
- Yi W, Hu X, Chen Z, Liu L, Tian Y, Chen H, Cong YS, Yang F, Zhang L, Rudolph KL, Zhang Z, Zhao Y, and Ju Z. Phosphatase Wip1 controls antigen-independent B-cell development in a p53-dependent manner. Blood. 2015 Jul 30;126(5):620-8. DOI:10.1182/blood-2015-02-624114 |
- Zajkowicz A, Butkiewicz D, Drosik A, Giglok M, Suwiński R, and Rusin M. Truncating mutations of PPM1D are found in blood DNA samples of lung cancer patients. Br J Cancer. 2015 Mar 17;112(6):1114-20. DOI:10.1038/bjc.2015.79 |
