p27kip1 Functional Regulation in Human Cancer: A Potential Target for Therapeutic Designs

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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, p27kip1, in human cancer, focusing in particular on the mechanisms underlying its functional inactivation in tumor cells. p27kip1 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 p27kip1 protein, rather than degraded, can be functionally inactivated. The mechanisms and the implications of these two types of p27kip1 deregulation will be discussed and some potential therapeutic approaches targeting p27kip1 functions will be proposed.

Keywords: adenoviral vectors; cell cycle regulation; cki; gene therapy; proteasome degradation; subcellular localization; tumor progression

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867054367149

Affiliations: Divisione di Oncologia Sperimentale 2, Centro di Riferimento Oncologico, Via Pedemontana occidentale, 12, 33081 Aviano, Italy.

Publication date: July 1, 2005

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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