title: SUMOylation and SUMO-interacting motif (SIM) of metastasis tumor antigen 1 (MTA1) synergistically regulate its transcriptional repressor function.
abstract: Metastasis tumor antigen 1 (MTA1), a component of the Mi-2·nucleosome remodeling and deacetylase complex, plays a crucial role in gene transcription, but the mechanism involved remains largely unknown. Here, we report that MTA1 is a substrate for small ubiquitin-related modifier 2/3 (SUMO2/3) in vivo. Protein inhibitor of activated STAT (PIAS) proteins enhance SUMOylation of MTA1 and may participate in paralog-selective SUMOylation, whereas sentrin/SUMO-specific protease 1 (SENP1) and 2 may act as deSUMOylation enzymes for MTA1. Moreover, MTA1 contains a functional SUMO-interacting motif (SIM) at its C terminus, and SIM is required for the efficient SUMOylation of MTA1. SUMO conjugation on Lys-509, which is located within the SUMO consensus site, together with SIM synergistically regulates the co-repressor activity of MTA1 on PS2 transcription, probably by recruiting HDAC2 onto the PS2 promoter. Interestingly, MTA1 may up-regulate the expression of SUMO2 via interaction with RNA polymerase II and SP1 at the SUMO2 promoter. These findings not only provide novel mechanistic insights into the regulation of the transcriptional repressor function of MTA1 by SUMOylation and SIM but also uncover a potential function of MTA1 in modulating the SUMOylation pathway.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, George Washington University, Washington, D. C. 20037.
authors.forename: Lin
authors.initials: L
authors.lastname: Cong
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, George Washington University, Washington, D. C. 20037.
authors.forename: Suresh B
authors.initials: SB
authors.lastname: Pakala
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, George Washington University, Washington, D. C. 20037.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Ohshiro
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, George Washington University, Washington, D. C. 20037.
authors.forename: Da-Qiang
authors.initials: DQ
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, George Washington University, Washington, D. C. 20037; Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, India. Electronic address: bcmrxk@gwumc.edu.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000737:chemistry*; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008239:Lysine / Q000737:chemistry; D008954:Models, Biological; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism*; D058207:Sumoylation; D015534:Trans-Activators
chemical_list: C089320:MTA1 protein, human; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D015534:Trans-Activators; D005982:Glutathione Transferase; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D008239:Lysine