Contrôle de la sortie de mitose par la protéine phosphatase Cdc14.

Abstract

Entre l' identification du mutant thermosensible cdc14 de la levure Saccharomyces cerevisiae, en 1981, et la fin de l' annee 1998, en passant par le clonage du gene en 1992, on avait appris assez peu de choses sur Cdc14. On savait que Cdc14 etait une proteine phosphatase chargee d' accomplir une tache essentielle en fin de mitose, apres la separation des chromatides soeurs en anaphase et avant l' inactivation du complexe universel de controle de la mitose, MPF (M-phase promoting factor). Cependant, quatre articles viennent d' etre publies entre decembre 1998 et avril 1999, qui nous renseignent maintenant sur la fonction et le mode de regulation de cette proteine phosphatase. Cdc14 a pour cible deux proteines, Sic1 et Hctl, qui sont directement impliquees dans l' inhibition du complexe MPF et la degradation des cyclines mitotiques. Cette fonction directement liee a l' activite catalytique de Cdc14 depend egalement de remaniements importants dans sa localisation intracellulaire, puisque celle-ci est sequestree dans le nucleole pendant la plus grande partie du cycle cellulaire et en est liberee au moment ou elle doit dephosphoryler ses cibles en fin de mitose.

Very little has been known on the Cdc14 phosphatase from the identification of the temperature-sensitive cdc14 mutant of the yeast Saccharomyces cerevisiae, in 1981, until the last few months. The sequence of the CDC14 protein, known since 1992, indicated a protein phosphatase signature. Analysis of the phenotype of the cdc14 mutant pointed out to an essential function of the phosphatase taking place somewhere during the end of mitosis, after separation of the sister chromatids but before inactivation of the Cdc2-cyclin B complex that controls mitosis in all eukaryotic cells. Recent studies conducted by four different research groups have now precisely documented Cdc14 function. Two targets of the phosphatase Cdc14 have thus been uncovered, namely Sic1 and Hct1/Cdh1, both of which had been previously implicated in inhibiting the Cdc2-cyclin B complex and inactivating mitotic cyclins. Cdc14 function is intimately dependent on its intracellular localization, since Cdc14 has been found to be sequestered within the nucleolus during most of the cell cycle and released from it precisely at the time needed to attain its targets, Sic1 and Hct1/Cdh1, at the end of mitosis.