Understanding p27(kip1) deregulation in cancer: down-regulation or mislocalization.
There is considerable evidence that the inactivation of the cyclin-dependent kinase inhibitor p27(kip1) is a fundamental step for the development of human malignancies. In particular, reduced expression of p27(kip1), due to increased protein degradation, correlates with poor prognosis of patients affected by various types of cancer. The purpose of this mini-review is to present an overview of the current understanding of the alteration of p27(kip1) function in human cancer and to describe the different mechanisms that contributes to it. Particular emphasis is placed on the novel finding of p27(kip1) mislocalization in tumor cells and on the biochemical pathways responsible for p27(kip1) cytosolic accumulation. Finally, we review the possible clinical implications of these observations with respect to prognosis and novel anticancer therapies.
Viglietto
Giuseppe
G
Instituto di Endocrinologia ed Oncologia Sperimentale, CNR & Dipartimento di Biologia e Patologie Cellulare e Molecolare, Naples, Italy. viglietto@sun.ceos.na.cnr.it
Motti
Maria Letizia
ML
Fusco
Alfredo
A
D000818:Animals; D002451:Cell Compartmentation / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003593:Cytoplasm / Q000201:enzymology; D015536:Down-Regulation / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000235:genetics
D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27