A negatively charged amino acid in Skp2 is required for Skp2-Cks1 interaction and ubiquitination of p27Kip1.
Proteolysis of cyclin-dependent kinase inhibitor p27 occurs predominantly in the late G1 phase of the cell cycle through a ubiquitin-mediated protein degradation pathway. Ubiquitination of p27 requires the SCFSkp2 ubiquitin ligase and Skp2 F-box binding protein Cks1. The mechanisms by which Skp2 recognizes Cks1 to ubiquitylate p27 remain obscure. Here ... we show that Asp-331 in the carboxyl terminus of Skp2 is required for its association with Cks1 and ubiquitination of p27. Mutation of Asp-331 to Ala disrupts the interaction between Skp2 and Cks1. Although Asp-331 mutation negates the ability of the Skp1-Cullin-F-box protein (SCF) complex to ubiquitylate p27, such a mutation has no effect on Skp2 self-ubiquitination. A conservative change from Asp to Glu at position 331 of Skp2 does not affect Skp2-Cks1 interaction. Our results revealed a unique requirement for a negatively charged residue in the carboxyl-terminal region of Skp2 in recognition of Cks1 and ubiquitination of p27.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Cell Cycle Proteins, Cell Line, Cyclin-Dependent Kinase Inhibitor p27, Humans, Models, Molecular, Molecular Sequence Data, Protein Binding, S-Phase Kinase-Associated Proteins, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Static Electricity, Tumor Suppressor Proteins, Ubiquitin
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Cell Cycle Proteins, Cell Line, Cyclin-Dependent Kinase Inhibitor p27, Humans, Models, Molecular, Molecular Sequence Data, Protein Binding, S-Phase Kinase-Associated Proteins, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Static Electricity, Tumor Suppressor Proteins, Ubiquitin
J. Biol. Chem.
Date: Aug. 22, 2003
PubMed ID: 12813041
View in: Pubmed Google Scholar
Download Curated Data For This Publication
1740
Switch View:
- Interactions 5