PPM1D regulates p21 expression via dephoshporylation at serine 123

Ruibing Cao, Jin Zhang, Min Zhang, Xinbin Chen

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The cyclin-dependent kinase inhibitor p21 plays a critical role in regulating cell cycle and cell proliferation. We previously cloned the dog p21 gene and found that unlike human p21, dog p21 is expressed as 2 isoforms due to the proline-directed phosphorylation at serine 123 (S123). Here, we identifi ed that PPM1D, also called Wip1 and a Mg2+-dependent phosphatase, dephosphorylates dog p21 protein at serine 123. Specifically, we showed that the level of S123-phosphorylated dog p21 is increased by a PPM1D inhibitor in a dose-dependent manner. We also showed that over-expression of PPM1D decreases, whereas knockdown of PPM1D increases, the level of S123-phosphorylated dog p21 regardless of p53. Additionally, in vitro phosphatase assay was performed and showed that phosphorylated S123 in dog p21 is dephosphorylated by recombinant rPPM1D, which contains the catalytic domain of human PPM1D (residue 1-420), but not by the phosphatase dead rPPM1D (D314A). Furthermore, dephosphorylation of S123 by rPPM1D can be abrogated by PPM1D inhibitor or by withdrawal of Mg2+. Finally, we showed that upon PPM1D inhibition, the level of S123-phosphorylated dog p21 was increased, concomitantly with decreased expression of cyclin A, cyclin B, Rb, and PCNA. Together, our results indicate that PPM1D functions as a phosphatase of dog p21 at serine 123 and plays a role in cell cycle control via p21.

Original languageEnglish (US)
Pages (from-to)641-647
Number of pages7
JournalCell Cycle
Volume14
Issue number4
DOIs
StatePublished - Feb 15 2015

Keywords

  • P21
  • P53
  • Phosphatase
  • PPM1D
  • Wip1

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'PPM1D regulates p21 expression via dephoshporylation at serine 123'. Together they form a unique fingerprint.

  • Cite this