Novel activation mechanism of macromolecular complex APC/C ubiquitin ligase

CDK1 and APC/C are two key regulatory enzymes controlling the cell division, growth, differentiation and death, through phosphorylation and ubiquitylation, respectively. Although it has long been apparent that phosphorylation modifies APC/C function, the challenges posed by the need for functional assays to study this control put the elucidation of molecular basis of phosphorylation control beyond our grasp. We recently overcame these limitations with a pipeline that uses reconstituted recombinant APC/C in Xenopus cell free extracts to show how CDK1 activates the APC/C through coordinated phosphorylation of Apc3 and Apc1. These results define a previously unrecognised subunit-subunit communication over a distance and the functional consequences of CDK phosphorylation of the APC/C, providing a new platform for studying dynamic regulation of the APC/C.