Common and specific roles of the related CDK inhibitors p27 and p57 revealed by a knock-in mouse model.
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. To elucidate the in vivo functions of these CKIs, we have now generated a knock-in mouse model (p57(p27KI)), in which the p57 gene has been replaced with the p27 gene. The p57(p27KI) mice are viable and appear healthy, with most of the developmental defects characteristic of p57(KO) mice having been corrected by p27 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.
Susaki
Etsuo
E
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
Nakayama
Keiko
K
Yamasaki
Lili
L
Nakayama
Keiichi I
KI
D000818:Animals; D017209:Apoptosis; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000502:physiology*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000172:deficiency / Q000502:physiology*; D050687:E2F1 Transcription Factor / Q000172:deficiency; D055879:Gene Knock-In Techniques; D048788:Growth and Development; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype
D050761:Cyclin-Dependent Kinase Inhibitor p57; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D050760:Cyclin-Dependent Kinase Inhibitor p27