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lüll Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer Frescas D; Pagano MNat Rev Cancer 2008[Jun]; 8 (6): 438-49The 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.|Animals[MESH]|Apoptosis Regulatory Proteins/metabolism[MESH]|Cell Cycle Proteins/physiology[MESH]|Co-Repressor Proteins[MESH]|Cullin Proteins/physiology[MESH]|Cyclin-Dependent Kinase Inhibitor p27/metabolism[MESH]|Cyclin-Dependent Kinases/metabolism[MESH]|DNA-Binding Proteins/metabolism[MESH]|Forkhead Box Protein O1[MESH]|Forkhead Transcription Factors/metabolism[MESH]|Humans[MESH]|NF-kappa B/metabolism[MESH]|Neoplasm Proteins/*metabolism[MESH]|Neoplasms/*metabolism[MESH]|Nerve Tissue Proteins/metabolism[MESH]|Oncogenes[MESH]|RNA-Binding Proteins/metabolism[MESH]|Repressor Proteins/metabolism[MESH]|S-Phase Kinase-Associated Proteins/*physiology[MESH]|SKP Cullin F-Box Protein Ligases/physiology[MESH]|beta-Transducin Repeat-Containing Proteins/*physiology[MESH]|cdc25 Phosphatases/metabolism[MESH] |