FIZZY IS REQUIRED FOR ACTIVATION OF THE APC CYCLOSOME IN XENOPUS EGG EXTRACTS/

The Xenopus homologue of Drosophila Fizzy and budding yeast CDC20 has been characterized. The encoded protein (X-FZY) is a component of a hi gh molecular weight complex distinct from the APC/cyclosome, Antibodie s directed against FZY were produced and shown to prevent calmodulin-d ependent protein kinase II (CaMKII) from inducing the metaphase to ana phase transition of spindles assembled irt vitro in Xenopus egg extrac ts, and this was associated with suppression of the degradation of mit otic cyclins. The same antibodies suppressed M phase-promoting factor (MPF)-dependent activation of the APC/cyclosome in interphase egg extr acts, although they did not appear to alter the pattern or extent of M PF-dependent phosphorylation of APC/cyclosome subunits, As these phosp horylations are thought to be essential for APC/cyclosome activation i n eggs and early embryos, we conclude that at least two events are req uired for MPF to activate the APC/cyclosome, allowing both chromatid s egregation and full degradation of mitotic cyclins. The first one, whi ch does not require FZY function, is the phosphorylation of APC/cyclos ome subunits, The second one, that requires FZY function (even in the absence of MAD2 protein and when the spindle assembly checkpoint is no t activated) is not yet understood at its molecular level.