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PMID: 8706131 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Cell ·Vol. 86 ·No. 2 ·1996-07-26 ·Pages 263-74

Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ

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.

MeSH Terms

Amino Acid Sequence Anaphase-Promoting Complex-Cyclosome Base Sequence Binding Sites/physiology Cell Cycle/genetics Cell Cycle Proteins/chemistry,genetics,metabolism,physiology Cyclins/chemistry,genetics,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

Chemicals

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

Authors & Affiliations

7 authors, click to expand affiliations / ORCID

Bai C

Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.

Sen P

Hofmann K

Ma L

Goebl M

Harper J W

Elledge S J

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(00)80098-7

Published

1996-07-26

Pages

263-74

Language

English

Region

United States

NLM ID

0413066

Subset

Grants

NIA NIH HHS · AG11085 · United States

NIGMS NIH HHS · GM44664 · United States

Databases

GENBANK

U61764

External Links

PubMed source DOI: 10.1016/s0092-8674(00)80098-7 View journal details

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

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