Signal-induced ubiquitination of p57(Kip2) is independent of the C-terminal consensus Cdk phosphorylation site.
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.
Leibovitch
Marie Pierre
MP
Laboratoire de Génétique Oncologique, UMR 8125 CNRS, 94805, Villejuif, France.
Kannengiesser
Caroline
C
Leibovitch
Serge Alexandre
SA
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D016384:Consensus Sequence; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D017434:Protein Structure, Tertiary; D013912:Threonine / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism*
C493965:Cdkn1c protein, mouse; D050761:Cyclin-Dependent Kinase Inhibitor p57; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D014452:Ubiquitins; D013912:Threonine; D018844:Cyclin-Dependent Kinases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex