Back
Full-text
Journal article

The F-box protein Skp2 is a ubiquitylation target of a Cul1-based core ubiquitin ligase complex: evidence for a role of Cul1 in the suppression of Skp2 expression in quiescent fibroblasts.

Show more…
  • 2000-10-18
Published in:
  • The EMBO journal. - 2000
Amino Acid Motifs
Amino Acid Sequence
Anaphase-Promoting Complex-Cyclosome
Animals
Cell Cycle Proteins
Cell Line
Cullin Proteins
Culture Media, Serum-Free
Cysteine Endopeptidases
Fibroblasts
Genetic Complementation Test
Humans
Ligases
Macromolecular Substances
Molecular Sequence Data
Multienzyme Complexes
Proteasome Endopeptidase Complex
Protein Binding
Protein Processing, Post-Translational
Protein Subunits
RNA, Messenger
Rats
Saccharomyces cerevisiae Proteins
Sequence Alignment
Suppression, Genetic
Ubiquitin-Protein Ligase Complexes
Ubiquitin-Protein Ligases
Ubiquitins
Yeasts
English The ubiquitin protein ligase SCF(Skp2) is composed of Skp1, Cul1, Roc1/Rbx1 and the F-box protein Skp2, the substrate-recognition subunit. Levels of Skp2 decrease as cells exit the cell cycle and increase as cells re-enter the cycle. Ectopic expression of Skp2 in quiescent fibroblasts causes mitogen-independent S-phase entry. Hence, mechanisms must exist for limiting Skp2 protein expression during the G(0)/G(1) phases. Here we show that Skp2 is degraded by the proteasome in G(0)/G(1) and is stabilized when cells re-enter the cell cycle. Rapid degradation of Skp2 in quiescent cells depends on Skp2 sequences that contribute to Cul1 binding and interference with endogenous Cul1 function in serum-deprived cells induces Skp2 expression. Furthermore, recombinant Cul1-Roc1/Rbx1-Skp1 complexes can catalyse Skp2 ubiquitylation in vitro. These results suggest that degradation of Skp2 in G(0)/G(1) is mediated, at least in part, by an autocatalytic mechanism involving a Skp2-bound Cul1-based core ubiquitin ligase and imply a role for this mechanism in the suppression of SCF(Skp2) ubiquitin protein ligase function during the G(0)/G(1) phases of the cell cycle.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/205295
Statistics
Document views: 57 File downloads:
  • Full-text: 0