Cell cycle regulation of the mammalian CDK activator RINGO/Speedy A

Dinarina, Ana; Santamaria, Patricia G.; Nebreda, Angel R.

doi:10.1016/j.febslet.2009.07.028

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Volume 583, Issue 17 , Pages 2772-2778, 3 September 2009

Cell cycle regulation of the mammalian CDK activator RINGO/Speedy A

Edited by Zhijie Chang

CNIO (Spanish National Cancer Center), Melchor Fernández Almagro 3, 28029 Madrid, Spain

Received 17 March 2009; received in revised form 30 June 2009; accepted 16 July 2009. published online 20 July 2009.

Abstract

Cell cycle progression is regulated by cyclin-dependent kinases (CDKs), whose activation requires the binding of regulatory subunits named cyclins. RINGO/Speedy A is a mammalian protein that has no amino acid sequence homology with cyclins but can activate CDKs. Here we show that RINGO/Speedy A is a highly unstable protein whose expression and phosphorylation are periodically regulated during the cell cycle. RINGO/Speedy A is degraded by the proteasome and the process involves the ubiquitin ligase SCF^Skp2. Overexpression of a stabilized RINGO/Speedy A form results in the accumulation of high levels of RINGO/Speedy A at late stages of mitosis, which interfere with cytokinesis and chromosome decondensation. Our data show that tight regulation of RINGO/Speedy A is important for the somatic cell cycle.

Structured summary

MINT-7226413:RINGO A (uniprotkb:Q5MJ70) physically interacts (MI:0914) with Ubiquitin (uniprotkb:P62988) by anti bait coimmunoprecipitation (MI:0006)MINT-7226431, MINT-7226448:RINGO A (uniprotkb:Q5MJ70) physically interacts (MI:0914) with Skp2 (uniprotkb:Q13309) by anti tag coimmunoprecipitation (MI:0007)