A reciprocal relationship between Rb and Skp2: implications for restriction point control, signal transduction to the cell cycle and cancer.
The identification of Skp2 as a direct E2F target has allowed us to document the existence of a positive feedback loop comprised of Rb-E2F, Skp2, p27 and cyclin E-cdk2. We have termed this set of regulatory molecules the Skp2 autoinduction loop. Interference with this loop selectively regulates cell cycle progression through the restriction point. We describe here how the Skp2 autoinduction loop may interact with other regulatory controls on the restriction point, and how the reciprocal relationship between Rb and Skp2 may affect signal transduction to the cell cycle and thinking about the role of Skp2 overexpression in cancers.
Assoian
Richard K
RK
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6084, USA. rka@pharm.med.upenn.edu
Yung
Yuval
Y
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000502:physiology*; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D018797:Cell Cycle Proteins; D016160:Retinoblastoma Protein; D044786:S-Phase Kinase-Associated Proteins