Article

CDK Inhibitors : Cell Cycle regulators and Beyond

Université de Toulouse - LBCMCP and CNRS - UMR5088, Toulouse, France.
Developmental Cell (Impact Factor: 9.71). 03/2008; 14(2):159-69. DOI: 10.1016/j.devcel.2008.01.013
Source: PubMed

ABSTRACT

First identified as cell cycle inhibitors mediating the growth inhibitory cues of upstream signaling pathways, the cyclin-CDK inhibitors of the Cip/Kip family p21Cip1, p27Kip1, and p57Kip2 have emerged as multifaceted proteins with functions beyond cell cycle regulation. In addition to regulating the cell cycle, Cip/Kip proteins play important roles in apoptosis, transcriptional regulation, cell fate determination, cell migration and cytoskeletal dynamics. A complex phosphorylation network modulates Cip/Kip protein functions by altering their subcellular localization, protein-protein interactions, and stability. These functions are essential for the maintenance of normal cell and tissue homeostasis, in processes ranging from embryonic development to tumor suppression.

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Available from: James M Roberts, Dec 17, 2013
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    • "Cyclin-dependent kinase (CDK) inhibitors (CKIs) act on various cyclin-CDK complexes during different phases of the cell cycle. Particularly, CKIs, such as p21 Cip1 , p27 Kip1 , and p57 Kip2 , have been shown to mediate the G1 arrest in response to an array of stimuli including DNA damage, mitogen deprivation, or drug treatments [19] [20] [21]. Here, we report a study on the effect of HDACIs on p27 Kip1 , a tight-binding inhibitor of CDK complexes, belonging to the Cip/Kip family. "
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    • "In addition, CDK activity is also regulated through their interaction with inhibitory proteins, such as p21 (also known as CDKN1A) and p27 (also known as CDKN1B). These proteins interact directly with the CDKs and inhibit the interaction with their regulatory cyclin (Besson et al., 2008). "
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    • "An important group of CDKI is the KIP/CIP family consisting of p21, p27 and p57. While these proteins share a similar N terminal structure, the remainder of their structure is sufficiently different that each may serve different functions [42]. Moreover, different mechanisms may control these CDKIs at different stages of the cell cycle. "
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