Cyclins in breast cancer: too much of a good thing.
Cyclin E, a key mediator of entry into the cell division cycle, is expressed abundantly in many breast cancers. However, amplification of the cognate gene is observed rarely, leaving the responsible mechanism(s) and its importance in tumorigenesis in doubt. In a recent report, Steve Reed's lab demonstrates that hCdc4/Fbw7 targets cyclin E for ubiquitin-mediated proteolysis and is mutant in a breast cancer cell line with high cyclin E levels. Independent work demonstrates that a Drosophila hCdc4 homologue constrains cyclin E expression in vivo. These results suggest that lesions in protein degradation pathways may contribute to cyclin E deregulation in breast cancer.
Enders
Greg H
GH
Penn/GI Division, Suite 600/CRB, 415 Curie Boulevard, Philadelphia, PA 19104-6144, USA. endersgh@mail.med.upenn.edu
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D002461:Cell Line, Transformed; D016213:Cyclins / Q000378:metabolism*; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D005656:Fungal Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases
C080443:CDC4 protein, S cerevisiae; D018797:Cell Cycle Proteins; D016213:Cyclins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D005656:Fungal Proteins; D009363:Neoplasm Proteins; D029701:Saccharomyces cerevisiae Proteins; D044767:Ubiquitin-Protein Ligases