Novel roles of Skp2 E3 ligase in cellular senescence, cancer progression, and metastasis.
S-phase kinase-associated protein 2 (Skp2) belongs to the F-box protein family. It is a component of the SCF E3 ubiquitin ligase complex. Skp2 has been shown to regulate cellular proliferation by targeting several cell cycle-regulated proteins for ubiquitination and degradation, including cyclin-dependent kinase inhibitor p27. Skp2 has also been demonstrated to display an oncogenic function since its overexpression has been observed in many human cancers. This review discusses the recent discoveries on the novel roles of Skp2 in regulating cellular senescence, cancer progression, and metastasis, as well as the therapeutic potential of targeting Skp2 for human cancer treatment.
Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Guocan
G
Wang
Chia-Hsin
CH
Chan
Yuan
Y
Gao
Hui-Kuan
HK
Lin
D000818:Animals; D002465:Cell Movement; D016922:Cellular Senescence; D003517:Cyclopentanes / Q000494:pharmacology; D018450:Disease Progression; D016503:Drug Delivery Systems / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D011743:Pyrimidines / Q000494:pharmacology; D044786:S-Phase Kinase-Associated Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D054875:Ubiquitination
D003517:Cyclopentanes; D011743:Pyrimidines; D044786:S-Phase Kinase-Associated Proteins; C539933:pevonedistat