Linked Life Data

18285455

Source:http://linkedlifedata.com/resource/pubmed/id/18285455

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-4-11
pubmed:abstractText
The Forkhead transcription factor FoxM1 is an important regulator of gene expression during the G(2) phase. Here, we show that FoxM1 transcriptional activity is kept low during G(1)/S through the action of its N-terminal autoinhibitory domain. We found that cyclin A/cdk complexes are required to phosphorylate and activate FoxM1 during G(2) phase. Deletion of the N-terminal autoinhibitory region of FoxM1 generates a mutant of FoxM1 (DeltaN-FoxM1) that is active throughout the cell cycle and no longer depends on cyclin A for its activation. Mutation of two cyclin A/cdk sites in the C-terminal transactivation domain leads to inactivation of full-length FoxM1 but does not affect the transcriptional activity of the DeltaN-FoxM1 mutant. We show that the intramolecular interaction of the N- and C-terminal domains depends on two RXL/LXL motifs in the C terminus of FoxM1. Mutation of these domains leads to a similar gain of function as deletion of the N-terminal repressor domain. Based on these observations we propose a model in which FoxM1 is kept inactive during the G(1)/S transition through the action of the N-terminal autorepressor domain, while phosphorylation by cyclin A/cdk complexes during G(2) results in relief of inhibition by the N terminus, allowing activation of FoxM1-mediated gene transcription.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-12482952, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-15024056, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-15531365, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-15654331, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-15671063, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-15817462, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-15958562, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-16314512, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-16504183, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-16875671, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-16913846, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-17891172, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-18034456, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-1943760, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-8290587, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-9032290, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-9108152, http://linkedlifedata.com/resource/pubmed/commentcorrection/18285455-9242644
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1098-5549
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3076-87
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Activation of FoxM1 during G2 requires cyclin A/Cdk-dependent relief of autorepression by the FoxM1 N-terminal domain.
pubmed:affiliation
Laboratory of Experimental Oncology, Department of Medical Oncology, University Medical Center, Stratenum 2.118, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. j.laoukili@amc.uva.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't