Abstract
Control of cyclin levels is critical for proper cell cycle regulation. In yeast, the stability of the G1 cyclin Cln1 is controlled by phosphorylation-dependent ubiquitination. Here it is shown that this reaction can be reconstituted in vitro with an SCF E3 ubiquitin ligase complex. Phosphorylated Cln1 was ubiquitinated by SCF (Skp1-Cdc53-F-box protein) complexes containing the F-box protein Grr1, Rbx1, and the E2 Cdc34. Rbx1 promotes association of Cdc34 with Cdc53 and stimulates Cdc34 auto-ubiquitination in the context of Cdc53 or SCF complexes. Rbx1, which is also a component of the von Hippel-Lindau tumor suppressor complex, may define a previously unrecognized class of E3-associated proteins.
MeSH Terms
Amino Acid Sequence
Anaphase-Promoting Complex-Cyclosome
Animals
Carrier Proteins/chemistry,metabolism
Cell Cycle Proteins/metabolism
Cell Line
Cullin Proteins
Cyclins/metabolism
F-Box Proteins
Fungal Proteins/metabolism
Ligases/metabolism
Molecular Sequence Data
Peptide Synthases/metabolism
Phosphorylation
Recombinant Fusion Proteins/metabolism
S-Phase Kinase-Associated Proteins
SKP Cullin F-Box Protein Ligases
Saccharomyces cerevisiae/metabolism
Saccharomyces cerevisiae Proteins
Sequence Alignment
Ubiquitin-Conjugating Enzymes
Ubiquitin-Protein Ligase Complexes
Ubiquitin-Protein Ligases
Ubiquitins/metabolism
Chemicals
CLN1 protein, S cerevisiae
Carrier Proteins
Cdc53 protein, S cerevisiae
Cell Cycle Proteins
Cullin Proteins
Cyclins
F-Box Proteins
Fungal Proteins
Recombinant Fusion Proteins
S-Phase Kinase-Associated Proteins
Saccharomyces cerevisiae Proteins
Ubiquitins
GRR1 protein, S cerevisiae
CDC34 protein, S cerevisiae
Ubiquitin-Conjugating Enzymes
Ubiquitin-Protein Ligase Complexes
Anaphase-Promoting Complex-Cyclosome
SKP Cullin F-Box Protein Ligases
Ubiquitin-Protein Ligases
Ligases
Peptide Synthases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Skowyra D
Verna and Marrs McLean Department of Biochemistry, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Koepp D M
Kamura T
Conrad M N
Conaway R C
Conaway J W
Elledge S J
Harper J W