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Science 17 October 1997:
Vol. 278. no. 5337, pp. 455 - 460
DOI: 10.1126/science.278.5337.455
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Reports

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, R. J. Deshaies

G1 cyclin-dependent kinase (Cdk)-triggered degradation of the S-phase Cdk inhibitor Sic1p has been implicated in the transition from G1 to S phase in the cell cycle of budding yeast. A multidimensional electrospray mass spectrometry technique was used to map G1 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 G1 extract, indicating that a primary function of G1 cyclins is to tag Sic1p for destruction. These data suggest a molecular model of how phosphorylation and proteolysis cooperate to bring about the G1/S transition in budding yeast.

R. Verma, G. Reynard, R. J. Deshaies, Division of Biology, Box 156-29, California Institute of Technology, Pasadena, CA 91125, USA. E-mail for R.J.D.: deshaies{at}cco.caltech.edu
R. S. Annan, M. J. Huddleston, S. A. Carr, Research Mass Spectrometry Laboratory, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.

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Pheromone-Dependent G1 Cell Cycle Arrest Requires Far1 Phosphorylation, but May Not Involve Inhibition of Cdc28-Cln2 Kinase, In Vivo.
A. Gartner, D.-I. Jeoung, S. Bourlat, F. R. Cross, and G. Ammerer (1998)
Mol. Cell. Biol. 18, 3681-3691
   Abstract »    Full Text »
Human CUL1 forms an evolutionarily conserved ubiquitin ligase complex (SCF) with SKP1 and an F-box protein.
S. A. Lyapina, C. C. Correll, E. T. Kipreos, and R. J. Deshaies (1998)
PNAS 95, 7451-7456
   Abstract »    Full Text »    PDF »
Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway.
Z. Dai, R. C. Quackenbush, K. D. Courtney, M. Grove, D. Cortez, G. W. Reuther, and A. M. Pendergast (1998)
Genes & Dev. 12, 1415-1424
   Abstract »    Full Text »
There's the Rub: a novel ubiquitin-like modification linked to cell cycle regulation.
M. Hochstrasser (1998)
Genes & Dev. 12, 901-907
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Cdc53 is a scaffold protein for multiple Cdc34/Skp1/F-box protein complexes that regulate cell division and methionine biosynthesis in yeast.
E. E. Patton, A. R. Willems, D. Sa, L. Kuras, D. Thomas, K. L. Craig, and M. Tyers (1998)
Genes & Dev. 12, 692-705
   Abstract »    Full Text »
The Cdk inhibitors p25rum1 and p40SIC1 are functional homologues that play similar roles in the regulation of the cell cycle in fission and budding yeast.
A Sanchez-Diaz, I Gonzalez, M Arellano, and S Moreno (1998)
J. Cell Sci. 111, 843-851
   Abstract »    PDF »
Characterization of the Net1 Cell Cycle-dependent Regulator of the Cdc14 Phosphatase from Budding Yeast.
E. E. Traverso, C. Baskerville, Y. Liu, W. Shou, P. James, R. J. Deshaies, and H. Charbonneau (2001)
J. Biol. Chem. 276, 21924-21931
   Abstract »    Full Text »    PDF »


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