Abstract

Dr Uttam Surana, , Principal Investigator, Institute of Molecular and Cell Biology, Singapore.



Centrosomes (spindle pole body in yeast) are the microtubule organizing centers (MTOC) of the mitotic spindle constituting its two poles and play prominent role in the symmetric segregation of chromosomes. Like chromosomes, the centrosome inherited from the progenitor cell duplicates once in each division cycle, following which the sister centrosomes segregate away from each other to assemble a short spindle at the onset of mitosis. Cdh1, an activator of the E3 ubiquitin ligase APC (Anaphase Promoting Complex), is a potent inhibitor of centrosome segregation and suppresses spindle assembly during S phase by mediating proteolytic destruction of the microtubule-associated proteins (MAPs) required to break the centrosome cohesion. Our recent studies suggest that a concerted action by two prominent kinases, Cdk1 and polo, is required to bring Cdh1-catalyzed destruction to a halt and to facilitate spindle assembly. In this scheme, phosphorylation of Cdh1 by Cdk1 creates a binding site for polo kinase which further phosphorylates Cdh1, causing its complete inactivation. Hence, Cdk1 acts as a priming-agent for the polo kinase. We will also briefly discuss how this control circuit involving Cdh1, Cdk1, polo and MAPs may be targeted by other cellular networks in contexts that demand restraining of spindle dynamics.