信号诱导的p57（Kip2）泛素化不依赖于C末端共有Cdk磷酸化位点。

Signal-induced ubiquitination of p57(Kip2) is independent of the C-terminal consensus Cdk phosphorylation site.

作者信息

Leibovitch Marie Pierre, Kannengiesser Caroline, Leibovitch Serge Alexandre

机构信息

Laboratoire de Génétique Oncologique, UMR 8125 CNRS, 94805, Villejuif, France.

出版信息

FEBS Lett. 2003 May 22;543(1-3):125-8. doi: 10.1016/s0014-5793(03)00425-3.

DOI:10.1016/s0014-5793(03)00425-3

PMID:12753918

Abstract

The cyclin-dependent kinase inhibitor p57(Kip2) is required for normal mouse embryonic development. p57(Kip2) consists of four structurally distinct domains in which the conserved C-terminal nuclear targeting domain contains a putative Cdk phosphorylation site (Thr(342)) that shares a great similitude in the adjacent sequences with p27(Kip1) but not with p21(Cip1). Phosphorylation on Thr(187) has been shown to promote degradation of p27(Kip1). Although there is sequence homology between the C-terminal part of p27(Kip1) and p57(Kip2), we show that the ubiquitination and degradation of p57(Kip2) are independent of Thr(342). In contrast a destabilizing element located in the N-terminal is implicated in p57(Kip2) destabilization.

摘要

细胞周期蛋白依赖性激酶抑制剂p57（Kip2）是正常小鼠胚胎发育所必需的。p57（Kip2）由四个结构不同的结构域组成，其中保守的C末端核靶向结构域包含一个假定的Cdk磷酸化位点（Thr（342）），该位点在相邻序列中与p27（Kip1）具有高度相似性，但与p21（Cip1）不同。已证明Thr（187）的磷酸化会促进p27（Kip1）的降解。尽管p27（Kip1）和p57（Kip2）的C末端部分存在序列同源性，但我们表明p57（Kip2）的泛素化和降解与Thr（342）无关。相反，位于N末端的一个不稳定元件与p57（Kip2）的不稳定有关。