p27(kip1) functional regulation in human cancer: a potential target for therapeutic designs.

Abstract:

:The mitotic cell cycle is a tightly regulated process that ensures the correct division of one cell into two daughter cells. Progress along the different phases of the cell cycle is positively regulated by the sequential activation of a family of serine-threonine kinases called CDKs (Cyclin Dependent Kinases). Their activity is counteracted by small proteins known as CDK inhibitors (CKI) that ensure the correct timing of CDK activation in the different phases of the cell cycle. The present review will deal with the role of one of this CKI, p27(kip1), in human cancer, focusing in particular on the mechanisms underlying its functional inactivation in tumor cells. p27(kip1) protein downregulation is usually achieved by proteasomal degradation and is often correlated to a worse prognosis in several types of human cancers, resulting in the reduction of disease free and overall survival. More recently, it has been proposed that p27(kip1) protein, rather than degraded, can be functionally inactivated. The mechanisms and the implications of these two types of p27(kip1) deregulation will be discussed and some potential therapeutic approaches targeting p27(kip1) functions will be proposed.

journal_name

Curr Med Chem

authors

Belletti B,Nicoloso MS,Schiappacassi M,Chimienti E,Berton S,Lovat F,Colombatti A,Baldassarre G

doi

10.2174/0929867054367149

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

1589-605

issue

14

eissn

0929-8673

issn

1875-533X

journal_volume

12

pub_type

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