Deregulated degradation of the cdk inhibitor p27 and malignant transformation.
p27 acts as a critical negative regulator of the cell cycle by inhibiting the activity of cyclin/cdk complexes during G0 and G1. Degradation of p27 is a critical event for the G1/S transition and occurs through ubiquitination by SCF(Skp2) and subsequent degradation by the 26S-proteasome. A tumor suppressing function of p27 has been demonstrated in mouse models and studies of human tumors. More recent evidence suggests that Skp2, the specific recognition factor for p27 ubiquitination, has oncogenic properties. This review will focus on the regulation of p27 proteolysis and its consequences for tumorigenesis.
Bloom
Joanna
J
Department of Pathology and NYU Cancer Instutute, MSB599, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Pagano
Michele
M
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D015398:Signal Transduction / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases