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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-4-16
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pubmed:abstractText |
The ubiquitin-mediated proteolysis of cyclin E plays a central role in cell-cycle progression, and cyclin E accumulation is a common event in cancer. Cyclin E degradation is triggered by multisite phosphorylation, which induces binding to the SCF(Fbw7) ubiquitin ligase complex. Structures of the Skp1-Fbw7 complex bound to cyclin E peptides identify a doubly phosphorylated pThr380/pSer384 cyclin E motif as an optimal, high-affinity degron and a singly phosphorylated pThr62 motif as a low-affinity one. Biochemical data indicate that the closely related yeast SCF(Cdc4) complex recognizes the multisite phosphorylated Sic1 substrate similarly and identify three doubly phosphorylated Sic1 degrons, each capable of high-affinity interactions with two Cdc4 phosphate binding sites. A model that explains the role of multiple cyclin E/Sic1 degrons is provided by the findings that Fbw7 and Cdc4 dimerize, that Fbw7 dimerization enhances the turnover of a weakly associated cyclin E in vivo, and that Cdc4 dimerization increases the rate and processivity of Sic1 ubiquitination in vitro.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CDC4 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin E,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/F-Box Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/S-Phase Kinase-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SIC1 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/SKP Cullin F-Box Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Threonine,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
131-43
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pubmed:dateRevised |
2010-12-28
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pubmed:meshHeading |
pubmed-meshheading:17434132-Amino Acid Sequence,
pubmed-meshheading:17434132-Binding Sites,
pubmed-meshheading:17434132-Cell Cycle Proteins,
pubmed-meshheading:17434132-Cell Line,
pubmed-meshheading:17434132-Cyclin E,
pubmed-meshheading:17434132-Cyclin-Dependent Kinase Inhibitor Proteins,
pubmed-meshheading:17434132-Dimerization,
pubmed-meshheading:17434132-F-Box Proteins,
pubmed-meshheading:17434132-Humans,
pubmed-meshheading:17434132-Models, Biological,
pubmed-meshheading:17434132-Molecular Sequence Data,
pubmed-meshheading:17434132-Phosphopeptides,
pubmed-meshheading:17434132-Phosphorylation,
pubmed-meshheading:17434132-Protein Binding,
pubmed-meshheading:17434132-Protein Structure, Tertiary,
pubmed-meshheading:17434132-S-Phase Kinase-Associated Proteins,
pubmed-meshheading:17434132-SKP Cullin F-Box Protein Ligases,
pubmed-meshheading:17434132-Saccharomyces cerevisiae,
pubmed-meshheading:17434132-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:17434132-Sequence Homology, Amino Acid,
pubmed-meshheading:17434132-Serine,
pubmed-meshheading:17434132-Structure-Activity Relationship,
pubmed-meshheading:17434132-Substrate Specificity,
pubmed-meshheading:17434132-Threonine,
pubmed-meshheading:17434132-Transfection,
pubmed-meshheading:17434132-Ubiquitin,
pubmed-meshheading:17434132-Ubiquitin-Protein Ligases
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pubmed:year |
2007
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pubmed:articleTitle |
Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases.
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pubmed:affiliation |
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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