Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer.
The maintenance and preservation of distinct phases during the cell cycle is a highly complex and coordinated process. It is regulated by phosphorylation--through the activity of cyclin-dependent kinases (CDKs)--and protein degradation, which occurs through ubiquitin ligases such as SCF (SKP1-CUL1-F-box protein) complexes and APC/C (anaphase-promoting complex/cyclosome). Here, we explore the functionality and biology of the F-box proteins, SKP2 (S-phase kinase-associated protein 2) and beta-TrCP (beta-transducin repeat-containing protein), which are emerging as important players in cancer biogenesis owing to the deregulated proteolysis of their substrates.
Frescas
David
D
Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Pagano
Michele
M
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000502:physiology; D056970:Co-Repressor Proteins; D044842:Cullin Proteins / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009857:Oncogenes; D016601:RNA-Binding Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000502:physiology*; D044843:SKP Cullin F-Box Protein Ligases / Q000502:physiology; D044844:beta-Transducin Repeat-Containing Proteins / Q000502:physiology*; D020687:cdc25 Phosphatases / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D056970:Co-Repressor Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D016328:NF-kappa B; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C114487:PDCD4 protein, human; C121019:RCOR1 protein, human; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D044786:S-Phase Kinase-Associated Proteins; D044844:beta-Transducin Repeat-Containing Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D044843:SKP Cullin F-Box Protein Ligases; D018844:Cyclin-Dependent Kinases; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases