spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
JCS ePress online publication date 25 Jan 2005
doi: 10.1242/jcs.01657

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.01657v1
118/4/795    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ma, R. Y.M.
Right arrow Articles by Yao, K.-M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ma, R. Y.M.
Right arrow Articles by Yao, K.-M.

Research Article

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


Richard Y.M. Ma, Tommy H.K. Tong, Alice M.S. Cheung, Anthony C.C. Tsang, Wai Ying Leung, and Kwok-Ming Yao*
* Author for correspondence (e-mail: kmyao{at}hkusua.hku.hk)

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.


This article has been cited by other articles:


Home page
 Molecular Cancer TherapeuticsHome page
J. M-M. Kwok, S. S. Myatt, C. M. Marson, R. C. Coombes, D. Constantinidou, and E. W-F. Lam
Thiostrepton selectively targets breast cancer cells through inhibition of forkhead box M1 expression
Mol. Cancer Ther., July 1, 2008; 7(7): 2022 - 2032.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. K. M. Li, D. K. Smith, W. Y. Leung, A. M. S. Cheung, E. W. F. Lam, G. P. Dimri, and K.-M. Yao
FoxM1c Counteracts Oxidative Stress-induced Senescence and Stimulates Bmi-1 Expression
J. Biol. Chem., June 13, 2008; 283(24): 16545 - 16553.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. Laoukili, M. Alvarez, L. A. T. Meijer, M. Stahl, S. Mohammed, L. Kleij, A. J. R. Heck, and R. H. Medema
Activation of FoxM1 during G2 Requires Cyclin A/Cdk-Dependent Relief of Autorepression by the FoxM1 N-Terminal Domain
Mol. Cell. Biol., May 1, 2008; 28(9): 3076 - 3087.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
A. Djamei, A. Pitzschke, H. Nakagami, I. Rajh, and H. Hirt
Trojan Horse Strategy in Agrobacterium Transformation: Abusing MAPK Defense Signaling
Science, October 19, 2007; 318(5849): 453 - 456.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
M. Shinohara, A. V. Mikhailov, J. A. Aguirre-Ghiso, and C. L. Rieder
Extracellular Signal-regulated Kinase 1/2 Activity Is Not Required in Mammalian Cells during Late G2 for Timely Entry into or Exit from Mitosis
Mol. Biol. Cell, December 1, 2006; 17(12): 5227 - 5240.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. A. Madureira, R. Varshochi, D. Constantinidou, R. E. Francis, R. C. Coombes, K.-M. Yao, and E. W.-F. Lam
The Forkhead Box M1 Protein Regulates the Transcription of the Estrogen Receptor {alpha} in Breast Cancer Cells
J. Biol. Chem., September 1, 2006; 281(35): 25167 - 25176.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
I.-M. Kim, T. Ackerson, S. Ramakrishna, M. Tretiakova, I-C. Wang, T. V. Kalin, M. L. Major, G. A. Gusarova, H. M. Yoder, R. H. Costa, et al.
The Forkhead Box m1 Transcription Factor Stimulates the Proliferation of Tumor Cells during Development of Lung Cancer
Cancer Res., February 15, 2006; 66(4): 2153 - 2161.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2005