Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Spruck, CH; Strohmaier, H; Sangfelt, O; Müller, HM; Hubalek, M; Müller-Holzner, E; Marth, C; Widschwendter, M; Reed, SI.
hCDC4 gene mutations in endometrial cancer.
Cancer Res. 2002; 62(16):4535-4539
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- Strohmaier Heimo
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- Abstract:
- Cyclin-dependent kinase 2 activated by cyclin E is involved in the initiation of DNA replication and other S phase functions. Consistent with this role, cyclin E protein accumulates at the G1-S phase transition and declines during early S phase. This profile of expression is the result of periodic transcription and ubiquitin-mediated proteolysis directed by SCF(hCdc4). However, in many types of human tumors cyclin E protein is elevated and deregulated relative to the cell cycle by an unknown mechanism. Here, we show that the F-box protein hCdc4 that targets cyclin E to the SCF (Skp1-Cull-F-box) protein ubiquitin ligase is mutated in at least 16% of human endometrial tumors. Mutations were found either in the substrate-binding domain of the protein or at the amino terminus, suggesting a critical role for the region of hCdc4 upstream of the F-box. hCDC4 gene mutations were accompanied by loss of heterozygosity and correlated with aggressive disease. The hCDC4 gene is localized to chromosome region 4q32, which is deleted in over 30% of human tumors. Our results show that the hCDC4 gene is mutated in primary human tumors and suggest that it may function as a tumor suppressor in the genesis of many human cancers.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenocarcinoma - genetics
- Blotting, Northern - genetics
- Cell Cycle Proteins - genetics
- Cyclin E - metabolism
- Endometrial Neoplasms - genetics
- F-Box Proteins - genetics
- Female - genetics
- Hela Cells - genetics
- Humans - genetics
- Mutation - genetics
- Reverse Transcriptase Polymerase Chain Reaction - genetics
- Ubiquitin-Protein Ligases - genetics