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Article: Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1c

TitleRaf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1c
Authors
KeywordsCyclin B1
FOXM1c
G2/M
Nucleocytoplasmic shuttling
Raf/MEK/MAPK
Issue Date2005
PublisherCompany of Biologists Ltd.
Citation
Journal Of Cell Science, 2005, v. 118 n. 4, p. 795-806 How to Cite?
AbstractThe forkhead box (FOX) transcription factor FOXM1 is ubiquitously expressed in proliferating cells. FOXM1 expression peaks at the G2/M phase of the cell cycle and its functional deficiency in mice leads to defects in mitosis. To investigate the role of FOXM1 in the cell cycle, we used synchronized hTERT-BJ1 fibroblasts to examine the cell cycle-dependent regulation of FOXM1 function. We observed that FOXM1 is localized mainly in the cytoplasm in cells at late-G1 and S phases. Nuclear translocation occurs just before entry into the G2/M phase and is associated with phosphorylation of FOXM1. Consistent with the dependency of FOXM1 function on mitogenic signals, nuclear translocation of FOXM1 requires activity of the Raf/MEK/MAPK signaling pathway and is enhanced by the MAPK activator aurintricarboxylic acid. This activating effect was suppressed by the MEK1/2 inhibitor U0126. In transient reporter assays, constitutively active MEK1 enhances the transactivating effect of FOXM1c, but not FOXM1b, on the cyclin B1 promoter. RT-PCR analysis confirmed that different cell lines and tissues predominantly express the FOXM1c transcript. Mutations of two ERK1/2 target sequences within FOXM1c completely abolish the MEK1 enhancing effect, suggesting a direct link between Raf/MEK/MAPK signaling and FOXM1 function. Importantly, inhibition of Raf/MEK/MAPK signaling by U0126 led to suppression of FOXM1 target gene expression and delayed progression through G2/M, verifying the functional relevance of FOXM1 activation by MEK1. In summary, we provide the first evidence that Raf/MEK/MAPK signaling exerts its G2/M regulatory effect via FOXM1c.
Persistent Identifierhttp://hdl.handle.net/10722/42622
ISSN
2015 Impact Factor: 4.706
2015 SCImago Journal Rankings: 3.501
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMa, RYMen_HK
dc.contributor.authorTong, THKen_HK
dc.contributor.authorCheung, AMSen_HK
dc.contributor.authorTsang, ACCen_HK
dc.contributor.authorLeung, WYen_HK
dc.contributor.authorYao, KMen_HK
dc.date.accessioned2007-03-23T04:28:05Z-
dc.date.available2007-03-23T04:28:05Z-
dc.date.issued2005en_HK
dc.identifier.citationJournal Of Cell Science, 2005, v. 118 n. 4, p. 795-806en_HK
dc.identifier.issn0021-9533en_HK
dc.identifier.urihttp://hdl.handle.net/10722/42622-
dc.description.abstractThe forkhead box (FOX) transcription factor FOXM1 is ubiquitously expressed in proliferating cells. FOXM1 expression peaks at the G2/M phase of the cell cycle and its functional deficiency in mice leads to defects in mitosis. To investigate the role of FOXM1 in the cell cycle, we used synchronized hTERT-BJ1 fibroblasts to examine the cell cycle-dependent regulation of FOXM1 function. We observed that FOXM1 is localized mainly in the cytoplasm in cells at late-G1 and S phases. Nuclear translocation occurs just before entry into the G2/M phase and is associated with phosphorylation of FOXM1. Consistent with the dependency of FOXM1 function on mitogenic signals, nuclear translocation of FOXM1 requires activity of the Raf/MEK/MAPK signaling pathway and is enhanced by the MAPK activator aurintricarboxylic acid. This activating effect was suppressed by the MEK1/2 inhibitor U0126. In transient reporter assays, constitutively active MEK1 enhances the transactivating effect of FOXM1c, but not FOXM1b, on the cyclin B1 promoter. RT-PCR analysis confirmed that different cell lines and tissues predominantly express the FOXM1c transcript. Mutations of two ERK1/2 target sequences within FOXM1c completely abolish the MEK1 enhancing effect, suggesting a direct link between Raf/MEK/MAPK signaling and FOXM1 function. Importantly, inhibition of Raf/MEK/MAPK signaling by U0126 led to suppression of FOXM1 target gene expression and delayed progression through G2/M, verifying the functional relevance of FOXM1 activation by MEK1. In summary, we provide the first evidence that Raf/MEK/MAPK signaling exerts its G2/M regulatory effect via FOXM1c.en_HK
dc.format.extent1167232 bytes-
dc.format.extent25088 bytes-
dc.format.mimetypeapplication/pdf-
dc.format.mimetypeapplication/msword-
dc.languageengen_HK
dc.publisherCompany of Biologists Ltd.en_HK
dc.relation.ispartofJournal of Cell Scienceen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectCyclin B1en_HK
dc.subjectFOXM1cen_HK
dc.subjectG2/Men_HK
dc.subjectNucleocytoplasmic shuttlingen_HK
dc.subjectRaf/MEK/MAPKen_HK
dc.subject.meshCell nucleus - metabolismen_HK
dc.subject.meshMap kinase signaling systemen_HK
dc.subject.meshTrans-activation (genetics)en_HK
dc.subject.meshTrans-activators - chemistry - metabolismen_HK
dc.subject.meshTranscription factors - chemistry - metabolismen_HK
dc.titleRaf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1cen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9533&volume=118&issue=pt 4&spage=795&epage=806&date=2005&atitle=Raf/MEK/MAPK+signaling+stimulates+the+nuclear+translocation+and+transactivating+activity+of+FOXM1cen_HK
dc.identifier.emailCheung, AMS:h9945256@graduate.hku.hken_HK
dc.identifier.emailYao, KM:kmyao@hku.hken_HK
dc.identifier.authorityCheung, AMS=rp01572en_HK
dc.identifier.authorityYao, KM=rp00344en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1242/jcs.01657en_HK
dc.identifier.pmid15671063-
dc.identifier.scopuseid_2-s2.0-14944357408en_HK
dc.identifier.hkuros97799-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-14944357408&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume118en_HK
dc.identifier.issue4en_HK
dc.identifier.spage795en_HK
dc.identifier.epage806en_HK
dc.identifier.isiWOS:000227741500015-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridMa, RYM=8323783700en_HK
dc.identifier.scopusauthoridTong, THK=8323783200en_HK
dc.identifier.scopusauthoridCheung, AMS=36985759800en_HK
dc.identifier.scopusauthoridTsang, ACC=7006979260en_HK
dc.identifier.scopusauthoridLeung, WY=7201504543en_HK
dc.identifier.scopusauthoridYao, KM=7403234578en_HK

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