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Vol. 88, No. 3-4, 2000
Issue release date: 2000
Cytogenet Cell Genet 88:255–258 (2000)

Five human genes encoding F-box proteins: chromosome mapping and analysis in human tumors

Chiaur D.S. · Murthy S. · Cenciarelli C. · Parks W. · Loda M. · Inghirami G. · Demetrick D. · Pagano M.
Departments of aPathology and bPediatrics, and cKaplan Comprehensive Cancer Center, New York University School of Medicine, New York, NY (USA); dDepartment of Pathology, University of Calgary, Calgary, Alberta (Canada); eDepartment of Adult Oncology, Dana-Farber Cancer Institute and Department of Pathology, Brigham & Women’s Hospital Boston, MA (USA)

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Members of the &Fumacr;-&bumacr;ox &pumacr;rotein (Fbp) family are characterized by an approximately 40 amino acid F-box motif. SCF complexes (formed by &Sumacr;kp1, &cumacr;ullin, and one of many &Fumacr;bps) act as protein-ubiquitin ligases that control the G1/S transition of the eukaryotic cell cycle. The substrate specificity of SCF complexes is determined by the presence of different Fbp subunits that recruit specific substrates for ubiquitination. Unchecked degradation of cellular regulatory proteins has been observed in certain tumors and it is possible that deregulated ubiquitin ligases play a role in the altered degradation of cell cycle regulators. We have recently identified a family of human Fbps. As a first step aimed at determining if FBP genes could be involved in human neoplasia, we have mapped the chromosome positions of 5 FBP genes by fluorescence in situ hybridization (FISH) to 10q24 (BTRC alias β-TRCP/FBW1a), 9q34 (FBXW2 alias FBW2), 13q22 (FBXL3A alias FBL3a), 5p12 (FBXO4 alias FBX4) and 6q25→q26 (FBXO5 alias FBX5). Since most of these are chromosomal loci frequently altered in tumors, we have screened 42 human tumor cell lines and 48 human tumor samples by Southern hybridization and FISH. While no gross alterations of the genes encoding β-Trcp/Fbw1a, Fbw2, Fbx4 and Fbx5 were found, heterozygous deletion of the FBXL3A gene was found in four of 13 small cell carcinoma cell lines. This is the first evaluation of genes encoding Fbps in human tumors.    

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