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

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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 SCFSkp2. 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). © 2009 Federation of European Biochemical Societies.

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Dinarina, A., Santamaria, P. G., & Nebreda, A. R. (2009). Cell cycle regulation of the mammalian CDK activator RINGO/Speedy A. FEBS Letters, 583(17), 2772–2778. https://doi.org/10.1016/j.febslet.2009.07.028

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