Publication Date:
2001-09-05
Description:
Cyclin E binds and activates the cyclin-dependent kinase Cdk2 and catalyzes the transition from the G1 phase to the S phase of the cell cycle. The amount of cyclin E protein present in the cell is tightly controlled by ubiquitin-mediated proteolysis. Here we identify the ubiquitin ligase responsible for cyclin E ubiquitination as SCFFbw7 and demonstrate that it is functionally conserved in yeast, flies, and mammals. Fbw7 associates specifically with phosphorylated cyclin E, and SCFFbw7 catalyzes cyclin E ubiquitination in vitro. Depletion of Fbw7 leads to accumulation and stabilization of cyclin E in vivo in human and Drosophila melanogaster cells. Multiple F-box proteins contribute to cyclin E stability in yeast, suggesting an overlap in SCF E3 ligase specificity that allows combinatorial control of cyclin E degradation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koepp, D M -- Schaefer, L K -- Ye, X -- Keyomarsi, K -- Chu, C -- Harper, J W -- Elledge, S J -- R01 AG011085/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2001 Oct 5;294(5540):173-7. Epub 2001 Aug 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX, 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11533444" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Motifs
;
Amino Acid Sequence
;
Animals
;
Breast Neoplasms/genetics/metabolism
;
*CDC2-CDC28 Kinases
;
*Cell Cycle
;
Cell Cycle Proteins/chemistry/genetics/*metabolism
;
Cell Line
;
Cyclin E/*metabolism
;
Cyclin-Dependent Kinase 2
;
Cyclin-Dependent Kinases/metabolism
;
Drosophila Proteins
;
Drosophila melanogaster
;
*F-Box Proteins
;
Humans
;
Mice
;
Molecular Sequence Data
;
Peptide Synthases/chemistry/genetics/*metabolism
;
Phosphorylation
;
Protein-Serine-Threonine Kinases/metabolism
;
RNA, Double-Stranded
;
Recombinant Fusion Proteins/metabolism
;
SKP Cullin F-Box Protein Ligases
;
Saccharomyces cerevisiae/genetics/metabolism
;
Saccharomyces cerevisiae Proteins
;
Sequence Alignment
;
Transfection
;
Tumor Cells, Cultured
;
*Ubiquitin-Protein Ligases
;
Ubiquitins/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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