Common and specific roles of the related CDK inhibitors p27 and p57 revealed by a knock-in mouse model

Etsuo Susaki, Keiko Nakayama, Lili Yamasaki, Keiichi I. Nakayama

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Although p27 and p57 are structurally related cyclin-dependent kinase inhibitors (CKIs), and are thought to perform similar functions, p27 knockout (p27 KO) and p57 KO mice show distinct phenotypes. Toelucidate theinvivo functionsofthese CKIs, wehave now generated a knock-in mouse model (p57 p27KI), in which the p57 gene has been replaced with the p27 gene. The p57 27KI mice are viable and appear healthy, with mostof the developmental defects characteristic ofp57 KOmice having been correctedbyp27 knock-in. Such developmental defects of p57 KO mice were also ameliorated in mice deficient in both p57 and the transcription factor E2F1, suggesting that loss of p57 promotes E2F1-dependent apoptosis. The developmental defects apparent in a few tissues of p57 KO mice were unaffected or only partially corrected by knock-in expression of p27. Thus, these observations indicate that p57 and p27 share many characteristics in vivo, but that p57 also performs specific functions not amenable to substitution with p27.

Original languageEnglish
Pages (from-to)5192-5197
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number13
DOIs
Publication statusPublished - Mar 31 2009

All Science Journal Classification (ASJC) codes

  • General

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