p27 associates with cyclin and cyclin-dependent kinase complexes to inhibit their kinase activity and contribute to the control of cell proliferation. p27 is phosphorylated on many sites, including threonine 187, in vivo, with the predominant phosphorylation site being serine 10. The extent of serine 10 phosphorylation by proline-directed kinase is markedly increased in cells in the G(0)-G(1) phase of the cell cycle compared to cells in the S or M phase. p27 concentration is regulated predominantly by post-translational mechanisms. p27 is degraded by both the ubiquitin-proteasome pathway and ubiquitinindependent proteolysis. Regulation of ubiquitin-mediated proteolysis is often achieved through ubiquitination of the targeted phosphorylated protein, which renders it more susceptible to degradation.