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

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) (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.