Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Strohmaier, H; Spruck, CH; Kaiser, P; Won, KA; Sangfelt, O; Reed, SI.
Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line.
Nature. 2001; 413(6853):316-322
Doi: 10.1038/35095076
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Strohmaier Heimo
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- Abstract:
- Cyclin E, one of the activators of the cyclin-dependent kinase Cdk2, is expressed near the G1-S phase transition and is thought to be critical for the initiation of DNA replication and other S-phase functions. Accumulation of cyclin E at the G1-S boundary is achieved by periodic transcription coupled with regulated proteolysis linked to autophosphorylation of cyclin E. The proper timing and amplitude of cyclin E expression seem to be important, because elevated levels of cyclin E have been associated with a variety of malignancies and constitutive expression of cyclin E leads to genomic instability. Here we show that turnover of phosphorylated cyclin E depends on an SCF-type protein-ubiquitin ligase that contains the human homologue of yeast Cdc4, which is an F-box protein containing repeated sequences of WD40 (a unit containing about 40 residues with tryptophan (W) and aspartic acid (D) at defined positions). The gene encoding hCdc4 was found to be mutated in a cell line derived from breast cancer that expressed extremely high levels of cyclin E.
- Find related publications in this database (using NLM MeSH Indexing)
- Amino Acid Sequence -
- Animals -
- Breast Neoplasms - genetics
- Cell Cycle Proteins - genetics
- Cyclin E - metabolism
- Expressed Sequence Tags - metabolism
- F-Box Proteins - metabolism
- Humans - metabolism
- Molecular Sequence Data - metabolism
- Mutation - metabolism
- Peptide Synthases - metabolism
- Phosphorylation - metabolism
- SKP Cullin F-Box Protein Ligases - metabolism
- Sequence Homology, Amino Acid - metabolism
- Tumor Cells, Cultured - metabolism
- Ubiquitin-Protein Ligases - metabolism
- Ubiquitins - metabolism
- Yeasts - metabolism