Sic1 stability is regulated by cdk-dependent phosphorylation

Keith Filer, Qinghua Chen, Michael Mendenhall

Research output: Contribution to journalArticlepeer-review


The Sic1 protein from budding yeast inhibits the activity of Cdc28 when complexed with B-type cyclins, particularly Clb5 and Clb6, which are needed for the initiation of DNA replication, but does not inhibit Cdc28 when complexed with Cln-type cyclins which are needed for budding and spindle pole body duplication. Sic1 is phosphorylated by Cdc28/Cln complexes, however. To determine what role Sic1 phosphorylation by Cdc28/Cln complexes may have on Sic1 function, we have systematically mutated all nine Cdc28 consensus phosphorylation sites in Sic1 (S/T-P sequences) to nonphosphorylatable residues. Phosphopeptide analyses indicate that most, if not all, of these sites are phosphorylated by Cdc28/Cln complexes in vitro. Each single mutation has an effect on cell cycle progression that is best explained as being caused by hyperstabilization of the Sic1 protein. Half life measurements of the individual mutant proteins are in agreement with this interpretation. A mutant allele of Sic1 lacking all nine consensus is still phosphorylated by Cdc28/Cln complexes indicating that Cdc28/Cln can phosphorylate Ser or Thr residues not followed by a Pro. These results support a model in which Sic1 acts to ensure that budding and spindle pole body duplication are initiated prior to DNA replication. Supported by NIH RO1 GM52527-01.

Original languageEnglish
Pages (from-to)A1387
JournalFASEB Journal
Issue number9
StatePublished - 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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