Regulation of Skp2 expression and activity and its role in cancer progression.
The regulation of cell cycle entry is critical for cell proliferation and tumorigenesis. One of the key players regulating cell cycle progression is the F-box protein Skp2. Skp2 forms a SCF complex with Skp1, Cul-1, and Rbx1 to constitute E3 ligase through its F-box domain. Skp2 protein levels are regulated during the cell cycle, and recent studies reveal that Skp2 stability, subcellular localization, and activity are regulated by its phosphorylation. Overexpression of Skp2 is associated with a variety of human cancers, indicating that Skp2 may contribute to the development of human cancers. The notion is supported by various genetic mouse models that demonstrate an oncogenic activity of Skp2 and its requirement in cancer progression, suggesting that Skp2 may be a novel and attractive therapeutic target for cancers.
Chan
Chia-Hsin
CH
1Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. cchan@mdanderson.org
Lee
Szu-Wei
SW
Wang
Jing
J
Lin
Hui-Kuan
HK
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D054875:Ubiquitination
D044786:S-Phase Kinase-Associated Proteins