The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy.
The cyclin-dependent kinase (Cdk) inhibitor p27 (also known as KIP1) regulates cell proliferation, cell motility and apoptosis. Interestingly, the protein can exert both positive and negative functions on these processes. Diverse post-translational modifications determine the physiological role of p27. Phosphorylation regulates p27 binding to and inhibition of cyclin-Cdk complexes, its localization and its ubiquitin-mediated proteolysis. In cancers, p27 is inactivated through impaired synthesis, accelerated degradation and by mislocalization. Moreover, studies in several tumour types indicate that p27 expression levels have both prognostic and therapeutic implications.
Chu
Isabel M
IM
Braman Family Breast Cancer Institute, and Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 1580 NW 10th Avenue, Miami, Florida 33136, USA.
Hengst
Ludger
L
Slingerland
Joyce M
JM
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis
D000970:Antineoplastic Agents; D050760:Cyclin-Dependent Kinase Inhibitor p27