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Phosphorylation of Sic1p by G_1 Cdk Required for Its Degradation and Entry into S Phase

Verma, R. and Annan, R. S. and Huddleston, M. J. and Carr, S. A. and Reynard, G. and Deshaies, R. J. (1997) Phosphorylation of Sic1p by G_1 Cdk Required for Its Degradation and Entry into S Phase. Science, 278 (5337). pp. 455-460. ISSN 0036-8075. http://resolver.caltech.edu/CaltechAUTHORS:20141203-080007204

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Abstract

G_1 cyclin-dependent kinase (Cdk)–triggered degradation of the S-phase Cdk inhibitor Sic1p has been implicated in the transition from G_1 to S phase in the cell cycle of budding yeast. A multidimensional electrospray mass spectrometry technique was used to map G_1 Cdk phosphorylation sites in Sic1p both in vitro and in vivo. A Sic1p mutant lacking three Cdk phosphorylation sites did not serve as a substrate for Cdc34p-dependent ubiquitination in vitro, was stable in vivo, and blocked DNA replication. Moreover, purified phosphoSic1p was ubiquitinated in cyclin-depleted G_1 extract, indicating that a primary function of G_1 cyclins is to tag Sic1p for destruction. These data suggest a molecular model of how phosphorylation and proteolysis cooperate to bring about the G_1/S transition in budding yeast.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.278.5337.455DOIArticle
http://www.sciencemag.org/content/278/5337/455PublisherArticle
ORCID:
AuthorORCID
Deshaies, R. J.0000-0002-3671-9354
Alternate Title:Phosphorylation of Sic1p by G1 Cdk Required for Its Degradation and Entry into S Phase
Additional Information:© 1997 American Association for the Advancement of Science. Received 16 June 1997; accepted 18 September 1997. We thank M. V. Castillo for MBP-SIC1, L. Johnston for Sic1p antiserum, S. Diamond for performing flow cytometry, J. Archer, B. Dunphy, and W. Shou for critically reading the manuscript, and members of the laboratory for helpful discussions. Supported in part by Searle/Chicago Community Trust and Lucille P. Markey Charitable Trust Scholar Awards to R.J.D. and by a grant from NIH (NIH RO1 GM52466-01).
Funders:
Funding AgencyGrant Number
Searle Scholars ProgramUNSPECIFIED
Lucille P. Markey Charitable TrustUNSPECIFIED
NIHRO1 GM52466-01
Chicago Community TrustUNSPECIFIED
Record Number:CaltechAUTHORS:20141203-080007204
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20141203-080007204
Official Citation:Phosphorylation of Sic1p by G1 Cdk Required for Its Degradation and Entry into S Phase R. Verma, R. S. Annan, M. J. Huddleston, S. A. Carr, G. Reynard, and R. J. Deshaies Science 17 October 1997: 278 (5337), 455-460. [DOI:10.1126/science.278.5337.455]
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52300
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:03 Dec 2014 21:00
Last Modified:07 Nov 2017 22:12

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