Linked Life Data

15671063

Source:http://linkedlifedata.com/resource/pubmed/id/15671063

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 4
pubmed:dateCreated
2005-2-9
pubmed:abstractText
The 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
795-806
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15671063-Active Transport, Cell Nucleus, pubmed-meshheading:15671063-Amino Acid Sequence, pubmed-meshheading:15671063-Animals, pubmed-meshheading:15671063-Cell Nucleus, pubmed-meshheading:15671063-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:15671063-Forkhead Transcription Factors, pubmed-meshheading:15671063-Humans, pubmed-meshheading:15671063-MAP Kinase Signaling System, pubmed-meshheading:15671063-Mice, pubmed-meshheading:15671063-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:15671063-Molecular Sequence Data, pubmed-meshheading:15671063-Phosphorylation, pubmed-meshheading:15671063-Protein Isoforms, pubmed-meshheading:15671063-Trans-Activators, pubmed-meshheading:15671063-Transcription Factors, pubmed-meshheading:15671063-Transcriptional Activation, pubmed-meshheading:15671063-raf Kinases
pubmed:year
2005
pubmed:articleTitle
Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1c.
pubmed:affiliation
Department of Biochemistry, Faculty of Medicine, The University of Hong Kong, 3/F Laboratory Block, The Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't