Post-translational regulation of the tumor suppressor p27KIP1
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Mitogenic signals stimulate cell division by activating cyclin/cyclin-dependent kinase (CDK) complexes. Their timely regulation ensures proper cell cycle progression. It is therefore not surprising that cyclin/CDK complexes are integrators of multiple signals from both the extracellular environment and intracellular cues. Important regulators of cyclin/CDKs are the CDK inhibitors that have attracted attention due to their association with disease. p27KIP1 is a CDK inhibitor that controls CDK activity throughout the cell cycle. As a CDK inhibitor, p27KIP1 has tumor suppressor activity. Besides CDKs, p27KIP1 regulates additional cellular processes, including cell motility, some of which seem to mediate oncogenic activities of p27KIP1. These activities of p27KIP1 are regulated through multiple phosphorylation sites, targeted by several signal transduction pathways. Understanding functions and regulation of p27KIP1 will be important to determine which isoform of p27KIP1 has anti- or pro-tumorigenic activities. Such knowledge might be of prognostic value and may offer novel therapeutic windows.