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Int. J. Mol. Sci. 2014, 15(6), 10233-10251; doi:10.3390/ijms150610233
Article

SUMOylation of FOXM1B Alters Its Transcriptional Activity on Regulation of MiR-200 Family and JNK1 in MCF7 Human Breast Cancer Cells

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Received: 28 April 2014; in revised form: 28 May 2014 / Accepted: 3 June 2014 / Published: 10 June 2014
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells 2014)
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Abstract: Transcription factor Forkhead Box Protein M1 (FOXM1) is a well-known master regulator in controlling cell-cycle pathways essential for DNA replication and mitosis, as well as cell proliferation. Among the three major isoforms of FOXM1, FOXM1B is highly associated with tumor growth and metastasis. The activities of FOXM1B are modulated by post-translational modifications (PTMs), such as phosphorylation, but whether it is modified by small ubiquitin-related modifier (SUMO) remains unknown. The aim of the current study was to determine whether FOXM1B is post-translationally modified by SUMO proteins and also to identify SUMOylation of FOXM1B on its target gene transcription activity. Here we report that FOXM1B is clearly defined as a SUMO target protein at the cellular levels. Moreover, a SUMOylation protease, SENP2, significantly decreased SUMOylation of FOXM1B. Notably, FOXM1B is selectively SUMOylated at lysine residue 463. While SUMOylation of FOXM1B is required for full repression of its target genes MiR-200b/c and p21, SUMOylation of FOXM1B is essential for full activation of JNK1 gene. Overall, we provide evidence that FOXM1B is post-translationally modified by SUMO and SUMOylation of FOXM1B plays a functional role in regulation of its target gene activities.
Keywords: FOXM1; SUMOylation; transcriptional activity; MiR-200b/c; JNK1 FOXM1; SUMOylation; transcriptional activity; MiR-200b/c; JNK1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Wang, C.-M.; Liu, R.; Wang, L.; Nascimento, L.; Brennan, V.C.; Yang, W.-H. SUMOylation of FOXM1B Alters Its Transcriptional Activity on Regulation of MiR-200 Family and JNK1 in MCF7 Human Breast Cancer Cells. Int. J. Mol. Sci. 2014, 15, 10233-10251.

AMA Style

Wang C-M, Liu R, Wang L, Nascimento L, Brennan VC, Yang W-H. SUMOylation of FOXM1B Alters Its Transcriptional Activity on Regulation of MiR-200 Family and JNK1 in MCF7 Human Breast Cancer Cells. International Journal of Molecular Sciences. 2014; 15(6):10233-10251.

Chicago/Turabian Style

Wang, Chiung-Min; Liu, Runhua; Wang, Lizhong; Nascimento, Leticia; Brennan, Victoria C.; Yang, Wei-Hsiung. 2014. "SUMOylation of FOXM1B Alters Its Transcriptional Activity on Regulation of MiR-200 Family and JNK1 in MCF7 Human Breast Cancer Cells." Int. J. Mol. Sci. 15, no. 6: 10233-10251.


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