UBIQUITINATION AND PROTEASOME MEDIATED DEGRADATION OF POLO-LIKE KINASE

Polo-like kinase (Plk) is a cell cycle-regulated, cyclin-independent s erine/threonine protein kinase. Plk protein levels are low or undetect able in terminally differentiated cells and tissues and its expression is strongly correlated with cell growth. Plk protein and enzymatic ac tivity are regulated by multiple mechanisms during cell cycle progress ion. During G(1) Plk levels are low but increasing amounts of protein are detected during S phase and the highest amounts during G(2)M. Tran scription of Plk message is specifically repressed during G(1) but tha t cannot entirely account for the rapid disappearance of Plk protein a t the end of mitosis. In this report we show that Plk protein can be d egraded in vitro by partially purified proteasomes and that specific p roteasome inhibitors can block Plk protein degradation both in vitro a nd in vivo. We also detected high molecular weight poly-ubiquitinated forms of Plk by immunoprecipitation and immunoblotting and confirmed t hat Plk, like other mitotic regulators, is targeted for destruction at the end of mitosis through the ubiquitin-proteasome mediated degradat ion pathway.