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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD
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Cadherins / genetics
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Cadherins / metabolism
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Cdc20 Proteins
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Cell Cycle / physiology*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cyclin-Dependent Kinases / genetics
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Cyclin-Dependent Kinases / metabolism*
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Enzyme Activation
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Humans
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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S-Phase Kinase-Associated Proteins / genetics
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S-Phase Kinase-Associated Proteins / metabolism
Substances
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Antigens, CD
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CDH1 protein, human
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Cadherins
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Cdc20 Proteins
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Cell Cycle Proteins
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RNA, Small Interfering
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Recombinant Fusion Proteins
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S-Phase Kinase-Associated Proteins
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SPDYA protein, human
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CDC20 protein, human
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Cyclin-Dependent Kinases