title: SUMOylation of FOXM1B alters its transcriptional activity on regulation of MiR-200 family and JNK1 in MCF7 human breast cancer cells.
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.
authors.affiliation: Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA. meowy200@yahoo.com.
authors.forename: Chiung-Min
authors.initials: CM
authors.lastname: Wang
authors.affiliation: Department of Genetics and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA. runhua@uab.edu.
authors.forename: Runhua
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Genetics and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA. lwang12@uab.edu.
authors.forename: Lizhong
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA. ln6739@stu.armstrong.edu.
authors.forename: Leticia
authors.initials: L
authors.lastname: Nascimento
authors.affiliation: Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA. v.brennan@umiami.edu.
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Brennan
authors.affiliation: Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA. yang_w@mercer.edu.
authors.forename: Wei-Hsiung
authors.initials: WH
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D000075223:Poly-ADP-Ribose Binding Proteins; D011401:Promoter Regions, Genetic; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D058207:Sumoylation; D014158:Transcription, Genetic
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; C485891:PIAS4 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D048055:Mitogen-Activated Protein Kinase 8; D003546:Cysteine Endopeptidases; C501833:SENP2 protein, human