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Gene Review: 

Ppm1d  -  protein phosphatase 1D magnesium-dependent...

Mus musculus

Synonyms: AV338790, PP2C-delta, Protein phosphatase 1D, Protein phosphatase 2C isoform delta, Protein phosphatase magnesium-dependent 1 delta, ...
 
 
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Disease relevance of Ppm1d

  • Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase [1].
  • A recent study using Wip1-deficient mice revealed that blocking its function significantly impaired RAS and ERBB2-induced breast tumor formation, suggesting that the inhibition of Wip1 could be a broad-spectrum treatment for breast cancer [2].
 

High impact information on Ppm1d

  • Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway [3].
  • In turn, deletion of the inhibitory ATM phosphatase, Wip1, results in ATM up-regulation and suppression of Emu-myc-induced B cell lymphomas [1].
  • The data are consistent with an important role for Wip1 in spermatogenesis, lymphoid cell function, and cell cycle regulation [4].
  • Mice lacking Wip1 show increased susceptibility to pathogens and diminished T- and B-cell function [4].
  • We show here that Wip1 message is expressed in moderate levels in all organs, but is present at very high levels in the testes, particularly in the postmeiotic round spermatid compartment of the seminiferous tubules [4].
 

Biological context of Ppm1d

  • Analysis of thymocyte subset numbers by flow cytometry suggested that cell numbers starting at the double-negative (DN)4 stage are significantly reduced in Wip1-deficient mice, and p53 activity is elevated in cell-sorted DN4 and double-positive subpopulations [5].
  • Fibroblasts derived from Wip1 null embryos have decreased proliferation rates and appear to be compromised in entering mitosis [4].
  • The mouse Wip1 gene is composed of six exons and spans over 36 kb of DNA [6].
  • Wip1 has been mapped near the p53 gene on mouse chromosome 11 [6].
  • Wip1-deficient mice are resistant to common cancer genes [2].
 

Anatomical context of Ppm1d

  • Analysis of young Wip1-deficient mice showed that they had fewer splenic T cells [5].
  • Expression of Wip1 mRNA was detected ubiquitously in adult and embryonic tissues, though expression in the testis was much higher than in other tissues [6].
 

Associations of Ppm1d with chemical compounds

  • The Wip1 gene is a serine/threonine phosphatase that is induced in a p53-dependent manner by DNA-damaging agents [4].
 

Other interactions of Ppm1d

References

  1. Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase. Shreeram, S., Hee, W.K., Demidov, O.N., Kek, C., Yamaguchi, H., Fornace, A.J., Anderson, C.W., Appella, E., Bulavin, D.V. J. Exp. Med. (2006) [Pubmed]
  2. Wip1-deficient mice are resistant to common cancer genes. Harrison, M., Li, J., Degenhardt, Y., Hoey, T., Powers, S. Trends in molecular medicine. (2004) [Pubmed]
  3. Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway. Bulavin, D.V., Phillips, C., Nannenga, B., Timofeev, O., Donehower, L.A., Anderson, C.W., Appella, E., Fornace, A.J. Nat. Genet. (2004) [Pubmed]
  4. Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control. Choi, J., Nannenga, B., Demidov, O.N., Bulavin, D.V., Cooney, A., Brayton, C., Zhang, Y., Mbawuike, I.N., Bradley, A., Appella, E., Donehower, L.A. Mol. Cell. Biol. (2002) [Pubmed]
  5. Wip1 phosphatase-deficient mice exhibit defective T cell maturation due to sustained p53 activation. Schito, M.L., Demidov, O.N., Saito, S., Ashwell, J.D., Appella, E. J. Immunol. (2006) [Pubmed]
  6. The structure and expression of the murine wildtype p53-induced phosphatase 1 (Wip1) gene. Choi, J., Appella, E., Donehower, L.A. Genomics (2000) [Pubmed]
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