SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box

Cell. 1996 Jul 26;86(2):263-74. doi: 10.1016/s0092-8674(00)80098-7.

Abstract

We have identified the yeast and human homologs of the SKP1 gene as a suppressor of cdc4 mutants and as a cyclin F-binding protein. Skp1p indirectly binds cyclin A/Cdk2 through Skp2p, and directly binds Skp2p, cyclin F, and Cdc4p through a novel structural motif called the F-box. SKP1 is required for ubiquitin-mediated proteolysis of Cin2p, Clb5p, and the Cdk inhibitor Sic1p, and provides a link between these molecules and the proteolysis machinery. A large number of proteins contain the F-box motif and are thereby implicated in the ubiquitin pathway. Different skp1 mutants arrest cells in either G1 or G2, suggesting a connection between regulation of proteolysis in different stages of the cycle.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Anaphase-Promoting Complex-Cyclosome
  • Base Sequence
  • Binding Sites / physiology
  • Cell Cycle / genetics
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / physiology
  • Cyclins / chemistry
  • Cyclins / genetics
  • Cyclins / metabolism
  • F-Box Proteins*
  • F-Box-WD Repeat-Containing Protein 7
  • Fungal Proteins / physiology
  • G1 Phase / physiology
  • G2 Phase / physiology
  • Gene Dosage
  • Gene Expression / physiology
  • Humans
  • Ligases / genetics
  • Mitosis / physiology
  • Molecular Sequence Data
  • Molecular Structure
  • Mutation / physiology
  • Protein Structure, Tertiary
  • Proteins / metabolism
  • S Phase / physiology
  • S-Phase Kinase-Associated Proteins
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin-Protein Ligase Complexes*
  • Ubiquitin-Protein Ligases*
  • Ubiquitins / physiology*
  • Yeasts / genetics

Substances

  • CCNF protein, human
  • CLN2 protein, S cerevisiae
  • Cell Cycle Proteins
  • Cyclins
  • F-Box Proteins
  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • Fungal Proteins
  • Proteins
  • S-Phase Kinase-Associated Proteins
  • Saccharomyces cerevisiae Proteins
  • Ubiquitins
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Ubiquitin-Protein Ligases
  • Ligases

Associated data

  • GENBANK/U61764