Role of serine 10 phosphorylation in p27 stabilization revealed by analysis of p27 knock-in mice harboring a serine 10 mutation

Yojiro Kotake, Keiko Nakayama, Noriko Ishida, Keiichi I. Nakayama

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

The inhibition of cyclin-dependent kinase activity by p27 contributes to regulation of cell cycle progression. Serine 10 is the major phosphorylation site of p27, and its phosphorylation has been shown to affect the stability and nuclear export of p27 at the G0-G1 transition in iransfected cultured cells. To investigate the physiological relevance of p27 phosphorylation on Ser10, we generated p27 "knock-in" mice that harbor an S10A mutation in this protein. Mice homozygous for the mutation (p27S10A/S10A mice) were normal in body size, but the abundance of p27 was decreased in many organs, including brain, thymus, spleen, and testis. The stability of p27 in G0 phase was markedly reduced in lymphocytes of p27S10A/S10A mice compared with that in wild-type cells, whereas p27 stability in S phase was similar in cells of the two genotypes. The degradation of p27 in cells of the mutant mice at G0 phase was prevented by a proteasome inhibitor. These data indicate that the physiological role of p27 phosphorylation on Ser10 is to stabilize the protein in G0 phase. Unexpectedly, the nuclear export of p27 at the G 0-G1 transition occurred normally in p27 S10A/S10A mouse embryonic fibroblasts, indicating that phosphorylation of Ser10 is dispensable for this process.

Original languageEnglish
Pages (from-to)1095-1102
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number2
DOIs
Publication statusPublished - 2005 Jan 14

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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