Cell-cyclin inhibitors: Three families united by common cause

Laboratory of Cell Cycle Regulation, Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Gene (Impact Factor: 2.14). 05/2000; 247(1-2):1-15. DOI: 10.1016/S0378-1119(00)00092-5
Source: PubMed


In the cellular program leading to DNA synthesis, signals that drive cells into S-phase converge at the level of CDK activity. The products of at least three different gene families, Ink4, Cip/Kip and the pRb pocket-protein family, suppress S-phase entry. Ink4 proteins act by antagonizing the formation and activation of cyclin D-CDK4 complexes, of which the ultimate downstream target as related to S-phase entry appears to be pRb. Cip/Kip inhibitors impinge upon that pathway by inhibiting CDK2 kinases that participate in the inactivation of pRb and, like cyclin E, may also have roles independent of pRb. How the activities of these three classes of proteins are coordinated remains obscure. In recent years, development of mouse models has accelerated the elucidation of this complex network, showing roles that are sometimes cooperative and sometimes overlapping. We will discuss the interrelationships between Cip/Kip inhibitors and the components of the pRb pathway, and how their activities ultimately regulate cell proliferation.

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Available from: Anxo Vidal, Oct 01, 2015
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    • "The CDK activity is negatively regulated by the interaction with specific CDK inhibitory proteins (CKIs) like p27Kip1. [29], [30] We showed that cyclin-dependent kinase inhibitor p27Kip1 was highly expressed in quiescent cells and high levels of p27Kip1 protein expression in RanGAP1 deficient cells. This is in accordance with findings from a balloon angioplasty study in rat arteries showing the induction of p27Kip1 in vascular SMCs and the contribution of p27Kip1 upregulation in the re-establishment of the quiescent phenotype. "
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    PLoS ONE 07/2014; 9(7):e101519. DOI:10.1371/journal.pone.0101519 · 3.23 Impact Factor
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    • "HDAC1 is a histone deacetylase that is able to inhibit the expression of cell cycle genes such as p21. By ubiquitination of HDAC1, CHFR is able to reverse HDAC1-induced repression of p21 and thereby restore the p21-G1 checkpoint [28, 30, 31]. Interestingly, CHFR was also shown to inhibit invasiveness and metastatic potential caused by HDAC1 expression by the regulation of metastasis suppressors, KAI1 and E-cadherin [28]. "
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    CANCER AND METASTASIS REVIEW 12/2013; 33(1). DOI:10.1007/s10555-013-9462-4 · 7.23 Impact Factor
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    • "Following exit from M-phase, Cdk1 activity remains suppressed during G1 phase by the association with Cdk-inhibitory proteins, a regulatory mechanism that will not be discussed further here (for a review see Vidal and Koff, 2000). "
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