In:
Cell Discovery, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2017-05-02)
Abstract:
Eukaryotic cell cycle progression through G 1 –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 G 1 –S transition due to the rapid clearance of G 1 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-Thr 173 by Mpk1 and inactivation of the Sic1-pThr 173 -targeting phosphatase (PP2A Cdc55 ) through greatwall kinase-activated endosulfines. Here we show that the Sic1-pThr 173 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.
Type of Medium:
Online Resource
ISSN:
2056-5968
DOI:
10.1038/celldisc.2017.12
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2017
detail.hit.zdb_id:
2842548-0
