PMID- 10828603 OWN - NLM STAT- MEDLINE DCOM- 20000626 LR - 20171101 IS - 0301-0171 (Print) IS - 0301-0171 (Linking) VI - 88 IP - 3-4 DP - 2000 TI - Five human genes encoding F-box proteins: chromosome mapping and analysis in human tumors. PG - 255-8 AB - Members of the F-box protein (Fbp) family are characterized by an approximately 40 amino acid F-box motif. SCF complexes (formed by Skp1, cullin, and one of many Fbps) act as protein-ubiquitin ligases that control the G(1)/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 beta-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 beta-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. CI - Copyright 2000 S. Karger AG, Basel FAU - Chiaur, D S AU - Chiaur DS AD - Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. FAU - Murthy, S AU - Murthy S FAU - Cenciarelli, C AU - Cenciarelli C FAU - Parks, W AU - Parks W FAU - Loda, M AU - Loda M FAU - Inghirami, G AU - Inghirami G FAU - Demetrick, D AU - Demetrick D FAU - Pagano, M AU - Pagano M LA - eng GR - CA66229/CA/NCI NIH HHS/United States GR - CA76584/CA/NCI NIH HHS/United States GR - GM57587/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - Switzerland TA - Cytogenet Cell Genet JT - Cytogenetics and cell genetics JID - 0367735 RN - EC 2.3.2.27 (SKP Cullin F-Box Protein Ligases) RN - EC 6.3.2.- (Peptide Synthases) SB - IM MH - Amino Acid Motifs MH - Blotting, Southern MH - Carcinoma, Small Cell/genetics MH - Chromosome Aberrations/genetics MH - Chromosome Deletion MH - Female MH - Genetic Testing MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lung Neoplasms/genetics MH - Male MH - Multigene Family/*genetics MH - Neoplasms/*genetics MH - Peptide Synthases/analysis/*chemistry/*genetics MH - *Physical Chromosome Mapping MH - SKP Cullin F-Box Protein Ligases MH - Tumor Cells, Cultured EDAT- 2000/06/01 09:00 MHDA- 2000/07/06 11:00 CRDT- 2000/06/01 09:00 PHST- 2000/06/01 09:00 [pubmed] PHST- 2000/07/06 11:00 [medline] PHST- 2000/06/01 09:00 [entrez] AID - 15532 [pii] AID - 10.1159/000015532 [doi] PST - ppublish SO - Cytogenet Cell Genet. 2000;88(3-4):255-8. doi: 10.1159/000015532.