TORC1 coordinates the conversion of Sic1 from a target to an inhibitor of cyclin-CDK-Cks1
- Moreno-Torres, Marta Department of Biology, University of Fribourg, Fribourg, Switzerland - Department of Biochemistry and Molecular Biology, University of Southern Denmark (SDU), Odense M, Denmark
- Jaquenoud, Malika Department of Biology, University of Fribourg, Fribourg, Switzerland
- Péli-Gulli, Marie-Pierre Department of Biology, University of Fribourg, Fribourg, Switzerland
- Nicastro, Raffaele Department of Biology, University of Fribourg, Fribourg, Switzerland
- De Virgilio, Claudio Department of Biology, University of Fribourg, Fribourg, Switzerland
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02.05.2017
Published in:
- Cell Discovery. - 2017, vol. 3, p. 17012
English
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.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Biologie
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 306213
- DOI 10.1038/celldisc.2017.12
- Persistent URL
- https://folia.unifr.ch/unifr/documents/306123
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