2016.02.24 The Activity and Stability of p21 is Regulated by Non-Receptor Tyrosine Kinases
Title: The Activity and Stability of p21 is Regulated by Non-Receptor Tyrosine Kinases
Speaker：Dr. Yongqi Huang
School of Chemistry and Chemical Engineering, Shandong University
Address： Rm 102, East wing of Old Chemistry Building, Peking Unversity
Chair： Prof. Zhirong Liu, Center for Quantitative Biology
The Cip/Kip family of cyclin-dependent kinase (Cdk) inhibitors includes p21Cip1, p27Kip1 and p57Kip2. Their kinase inhibitory activities are mediated by a homologous N-terminal kinase-inhibitory domain (KID). The Cdk inhibitory activity and stability of p27 have been shown to be regulated by a two-step phosphorylation mechanism involving a tyrosine residue within the KID and a threonine residue within the flexible C-terminus. We show that these residues are conserved in p21 and p57, suggesting that a similar phosphorylation cascade regulates these Cdk inhibitors. However, the presence of a cyclin binding motif within its C-terminus alters the regulatory interplay between p21 and Cdk2/cyclin A, and its responses to tyrosine phosphorylation and altered p21:Cdk2/cyclin A stoichiometry. Although the Cip/Kip proteins can be phosphorylated in vitro by representatives of many non-receptor tyrosine kinase (NRTK) sub-families, the stability of p21 is not related to tyrosine phosphorylation in cell based experiments, suggesting that the stability and activity of Cip/Kip proteins are regulated via different mechanisms.