Source:http://linkedlifedata.com/resource/pubmed/id/12764136
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
31
|
| pubmed:dateCreated |
2003-7-28
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| pubmed:abstractText |
One of the major regulators of mitosis in somatic cells is cdc25B. cdc25B is tightly regulated at multiple levels. The final activation step involves the regulated binding of 14-3-3 proteins. Previous studies have demonstrated that Ser-323 is a primary 14-3-3 binding site in cdc25B, which influences its activity and cellular localization. 14-3-3 binding to this site appeared to interact with the N-terminal domain of cdc25B to regulate its activity. The presence of consensus 14-3-3 binding sites in the N-terminal domain suggested that the interaction is through direct binding of the 14-3-3 dimer to sites in the N-terminal domain. We have identified Ser-151 and Ser-230 in the N-terminal domain as functional 14-3-3 binding sites utilized by cdc25B in vivo. These low affinity sites cooperate to bind the 14-3-3 dimer bound to the high affinity Ser-323 site, thus forming an intramolecular bridge that constrains cdc25B structure to prevent access of the catalytic site. Loss of 14-3-3 binding to either N-terminal site relaxes cdc25B structure sufficiently to permit access to the catalytic site, and the nuclear export sequence located in the N-terminal domain. Mutation of the Ser-323 site was functionally equivalent to the mutation of all three sites, resulting in the complete loss of 14-3-3 binding, increased access of the catalytic site, and access to nuclear localization sequence.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/14-3-3 Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CDC25B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine 3-Monooxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/cdc25 Phosphatases
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
278
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
28580-7
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| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:12764136-14-3-3 Proteins,
pubmed-meshheading:12764136-Animals,
pubmed-meshheading:12764136-Binding Sites,
pubmed-meshheading:12764136-COS Cells,
pubmed-meshheading:12764136-Catalysis,
pubmed-meshheading:12764136-Cell Cycle Proteins,
pubmed-meshheading:12764136-Cell Line,
pubmed-meshheading:12764136-Cell Nucleus,
pubmed-meshheading:12764136-Cytoplasm,
pubmed-meshheading:12764136-Dimerization,
pubmed-meshheading:12764136-Fluorescent Antibody Technique,
pubmed-meshheading:12764136-Gene Expression,
pubmed-meshheading:12764136-HeLa Cells,
pubmed-meshheading:12764136-Humans,
pubmed-meshheading:12764136-Immunoblotting,
pubmed-meshheading:12764136-Immunosorbent Techniques,
pubmed-meshheading:12764136-Mutagenesis, Site-Directed,
pubmed-meshheading:12764136-Peptide Fragments,
pubmed-meshheading:12764136-Point Mutation,
pubmed-meshheading:12764136-Structure-Activity Relationship,
pubmed-meshheading:12764136-Transfection,
pubmed-meshheading:12764136-Tyrosine 3-Monooxygenase,
pubmed-meshheading:12764136-cdc25 Phosphatases
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| pubmed:year |
2003
|
| pubmed:articleTitle |
14-3-3 acts as an intramolecular bridge to regulate cdc25B localization and activity.
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| pubmed:affiliation |
Cancer Biology Program, Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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