Regulation of CIP/KIP cell cycle inhibitors and their biological implications

Order of Publishing in Issue: 
Volume :3
Issue :2
April, 2009
Page No: 
Jinhwa Lee
Dept. of Clinical Lab Science, Dongseo University, Busan 617-716, Korea

The cell cycle regulation is a keyhomeostatic device upon the cellular decisionduring the multi processes like proliferation,differentiation, survival and death. Humancancers can arise from the result of functionalfailure in cell cycle regulators. Therefore, activityof the major cell cycle regulator, cyclin-dependentkinase (CDK), is tightly regulated by cyclindependent kinase inhibitors (CKIs) such as thep21CIP1 and p27KIP1. These CKIs, mainlyfunctioning as a cyclinE/CDK2 complex inhibitorduring the G1 cell cycle, have been reported toplay disparate roles including the assembly ofcyclinD/CDK4,6 and others that apparently assistcell growth if not help carcinogenesis. While theirgenetic disruptions are rarely found in humancancers, low expression levels or cytoplasmicmislocalizations of the p21CIP1 and p27KIP1often correlate with human malignancies. Recentstudies show that signalling kinases can directlyphosphorylate these proteins as a substrate andchange their activities in the role of a cell cycleinhibitor by switching interacting partner proteinsafter the phosphorylation-driven structuralmodifications. This report will discuss the complexregulatory mechanisms of p21CIP1 and p27KIP1proteins on the cue of extracellular signals andtheir indications of functional importance tocarcinogenesis.

Cell cycle; Proliferation; CDK, p21CIP1, p27KIP1
Paper-2.pdf43.75 KB

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