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TORC1 coordinates the conversion of Sic1 from a target to an inhibitor of cyclin-CDK-Cks1

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TORC1 coordinates the conversion of Sic1 from a target to an inhibitor of cyclin-CDK-Cks1

dc.contributor.author	Moreno Torres, Marta
dc.contributor.author	Jaquenoud, Malika
dc.contributor.author	Péli Gulli, Marie Pierre
dc.contributor.author	Nicastro, Raffaele
dc.contributor.author	De Virgilio, Claudio
dc.date.accessioned	2023-05-22T06:50:16Z
dc.date.available	2023-05-22T06:50:16Z
dc.date.issued	2017
dc.identifier.citation	Moreno Torres, Marta Jaquenoud, Malika Péli Gulli, Marie Pierre Nicastro, Raffaele De Virgilio, Claudio 2017 TORC1 coordinates the conversion of Sic1 from a target to an inhibitor of cyclin-CDK-Cks1 Cell Discovery 17012 1 12
dc.identifier.uri	https://hdl.handle.net/10550/86738
dc.description.abstract	Eukaryotic cell cycle progression through G1-S is driven by hormonal and growth-related signals that are transmitted by the target of rapamycin complex 1 (TORC1) pathway. In yeast, inactivation of TORC1 restricts G1-S transition due to the rapid clearance of G1 cyclins (Cln) and the stabilization of the B-type cyclin (Clb) cyclin-dependent kinase (CDK) inhibitor Sic1. The latter mechanism remains mysterious but requires the phosphorylation of Sic1-Thr173 by Mpk1 and inactivation of the Sic1-pThr173-targeting phosphatase (PP2ACdc55) through greatwall kinase-activated endosulfines. Here we show that the Sic1-pThr173 residue serves as a specific docking site for the CDK phospho-acceptor subunit Cks1 that sequesters, together with a C-terminal Clb5-binding motif in Sic1, Clb5-CDK-Cks1 complexes, thereby preventing them from flagging Sic1 for ubiquitin-dependent proteolysis. Interestingly, this functional switch of Sic1 from a target to an inhibitor of cyclin-CDK-Cks1 also operates in proliferating cells and is coordinated by the greatwall kinase, which responds to both Cln-CDK-dependent cell-cycle and TORC1-mediated nutritional cues.
dc.language.iso	eng
dc.relation.ispartof	Cell Discovery, 2017, num. 17012, p. 1-12
dc.subject	Bioquímica
dc.subject	Biologia
dc.title	TORC1 coordinates the conversion of Sic1 from a target to an inhibitor of cyclin-CDK-Cks1
dc.type	journal article
dc.date.updated	2023-05-22T06:50:16Z
dc.identifier.doi	10.1038/celldisc.2017.12
dc.identifier.idgrec	158856
dc.rights.accessRights	open access