Abstract
In numerous instances, the fate of a single cell not only represents its peculiar outcome but also contributes to the overall status of an organism. In turn, the cell division cycle and its control strongly influence cell destiny, playing a critical role in targeting it towards a specific phenotype. Several factors participate in the control of growth, and among them, p27Kip1 and p57Kip2, two proteins modulating various transitions of the cell cycle, appear to play key functions. In this review, the major features of p27 and p57 will be described, focusing, in particular, on their recently identified roles not directly correlated with cell cycle modulation. Then, their possible roles as molecular effectors of polyphenols’ activities will be discussed. Polyphenols represent a large family of natural bioactive molecules that have been demonstrated to exhibit promising protective activities against several human diseases. Their use has also been proposed in association with classical therapies for improving their clinical effects and for diminishing their negative side activities. The importance of p27Kip1 and p57Kip2 in polyphenols’ cellular effects will be discussed with the aim of identifying novel therapeutic strategies for the treatment of important human diseases, such as cancers, characterized by an altered control of growth.
Highlights
During the last two decades, polyphenols have gained huge interest as potential adjuvant cancer drugs and cancer-preventing molecules
P27/p57 originally became popular in the field of cell cycle regulation for their pivotal role as CDK inhibitors (CDKIs), their cyclin-dependent kinase (CDK)-unrelated functions are increasingly maturing towards the control of multiple complex processes that include apoptosis, autophagy, DNA-damage repair, gene transcriptional control, cytoskeleton remodeling, and many others, as we largely described in the above sections
It is conceivable to expect an increase in their levels, together with those of other possible inhibitors of cell proliferation, because of the upstream events triggered by polyphenols, ending up with cell cycle arrest
Summary
During the last two decades, polyphenols have gained huge interest as potential adjuvant cancer drugs and cancer-preventing molecules. The protein seems to exert an anti-apoptotic function mainly related to the ability of the C-terminal domain of p57 to bind and inhibit JNK activities in a CDK-independent manner [20]. The signals proceed towards the JNK-dependent activation of transcription factors that drive apoptotic processes and/or block cell proliferation In this context, the inhibitory action of p57 could be an important mechanism by which the protein exerts its function on processes such as cell death and differentiation [20,111].
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