title: High mobility group nucleosomal binding domain 2 (HMGN2) SUMOylation by the SUMO E3 ligase PIAS1 decreases the binding affinity to nucleosome core particles.
abstract: High mobility group nucleosomal binding domain 2 (HMGN2) is a small and unique non-histone protein that has many functions in a variety of cellular processes, including regulation of chromatin structure, transcription, and DNA repair. In addition, it may have other roles in antimicrobial activity, cell homing, and regulating cytokine release. Although the biochemical properties of HMGN2 protein are regulated by acetylation and phosphorylation, it is not yet known whether HMGN2 activity can also be regulated by SUMOylation. In this study, we demonstrated for the first time that HMGN2 is modified by covalent attachment of small ubiquitin-related modifier 1 (SUMO1) by pro-inflammatory signal and identified the major SUMOylated lysine residues that localize to the HMGN2 nucleosome-binding domain at Lys-17 and Lys-35. SENP1 can deSUMOylate SUMOylated HMGN2, and PIAS1 is the E3 ligase responsible for SUMOylation of HMGN2. Finally, using SUMO1-conjugated HMGN2 purified from a basal SUMOylation system in Escherichia coli, we demonstrated that SUMOylated HMGN2 has decreased the binding affinity to nucleosome core particles in comparison to unSUMOylated HMGN2. These observations potentially provide new perspectives for understanding the functions of HMGN2 in inflammatory reaction.
authors.affiliation: From the Department of Microbiology, Brain Korea 21 Plus Project for Medical Science, the Laboratory of Medical Genetics, Harbin Medical University, Harbin 150086, China, and.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: From the Department of Microbiology.
authors.forename: Sol
authors.initials: S
authors.lastname: Kim
authors.affiliation: From the Department of Microbiology.
authors.forename: Man Sup
authors.initials: MS
authors.lastname: Kwak
authors.affiliation: From the Department of Microbiology, Brain Korea 21 Plus Project for Medical Science.
authors.forename: Jang Bin
authors.initials: JB
authors.lastname: Jeong
authors.affiliation: From the Department of Microbiology, Brain Korea 21 Plus Project for Medical Science.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Min
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Ho-Geun
authors.initials: HG
authors.lastname: Yoon
authors.affiliation: the Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
authors.forename: Jin-Hyun
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: From the Department of Microbiology, Brain Korea 21 Plus Project for Medical Science, Severance Biomedical Science Institute and Institute for Immunology and Immunological Diseases, and jsshin6203@yuhs.ac.
authors.forename: Jeon-Soo
authors.initials: JS
authors.lastname: Shin
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D024242:HMGN2 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000737:chemistry; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D024242:HMGN2 Protein; D009707:Nucleosomes; C106529:PIAS1 protein, human; D050828:Protein Inhibitors of Activated STAT; D011994:Recombinant Proteins; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D044767:Ubiquitin-Protein Ligases; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases; D008239:Lysine
keywords: Chromatin Regulation; HMGN2; Inflammation; Molecular Cell Biology; Nucleosome; Sumoylation