CDK Inhibitors: Cell Cycle Regulators and Beyond

Université de Toulouse - LBCMCP and CNRS - UMR5088, Toulouse, France.
Developmental Cell (Impact Factor: 10.37). 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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    • "These data suggest that CPR5 and SIM/SMR1 may signal through E2F during the plant immune response. SIAMESE/SIAMESE-RELATED 1 and E2F Are Required for Pathogen Effector-Triggered Programmed Cell Death and Immunity Our microarray data suggest that like mammalian Cip/Kip proteins , which are known to play a key role in integrating stress signals into cell fate determination (Besson et al., 2008), plant CKIs and E2Fs may be important regulators of PCD in response to pathogen challenge. This is consistent with the genetic data showing that the cpr5-associated PCD in cotyledons was fully suppressed by both sim smr1 and e2fabc (Figures 3A and 3B). "
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    • "Interestingly, TGFb signaling stimulates the expression of p57 at the mRNA and protein levels in different cell types (Chen et al., 2006; Scandura et al., 2004), including renal tubular cells (Sinuani et al., 2009). Consistent with its function as a CDK inhibitor, overexpression of p57 causes G1/S cell cycle arrest in cultured cells by preferential binding to CDK2 (Besson et al., 2008) or to CDK1, thereby inducing endoreplication (Ullah et al., 2009). More recently it has been reported that p57 integrates stress signals into cell cycle progression to promote cell survival in response to various types of injuries, including oxidative stress (Joaquin et al., 2012). "
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    • "Cell cycle exit in muscle cells is orchestrated by cyclin-dependent kinase inhibitors (CDKIs) belonging to the CIP/Kip family: p21 cip1 (Cdkn1a, p21 waf1 ), p27 kip1 (Cdkn1b) and p57 kip2 (Cdkn1c), abbreviated here as p21, p27 and p57, respectively. These CDKIs can bind and inhibit all combinations of cyclin-CDK complexes (reviewed by Besson et al., 2008). Most notably, in the absence of both p21 and p57, skeletal muscle development is severely affected and fiber formation is impaired, with myogenic cells undergoing apoptosis. "
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