title: SUMO5, a Novel Poly-SUMO Isoform, Regulates PML Nuclear Bodies.
abstract: Promyelocytic leukemia nuclear bodies (PML-NBs) are PML-based nuclear structures that regulate various cellular processes. SUMOylation, the process of covalently conjugating small ubiquitin-like modifiers (SUMOs), is required for both the formation and the disruption of PML-NBs. However, detailed mechanisms of how SUMOylation regulates these processes remain unknown. Here we report that SUMO5, a novel SUMO variant, mediates the growth and disruption of PML-NBs. PolySUMO5 conjugation of PML at lysine 160 facilitates recruitment of PML-NB components, which enlarges PML-NBs. SUMO5 also increases polySUMO2/3 conjugation of PML, resulting in RNF4-mediated disruption of PML-NBs. The acute promyelocytic leukemia oncoprotein PML-RARα blocks SUMO5 conjugation of PML, causing cytoplasmic displacement of PML and disruption of PML-NBs. Our work not only identifies a new member of the SUMO family but also reveals the mechanistic basis of the PML-NB life cycle in human cells.
authors.affiliation: Institute of Molecular Biology, National Chung Hsing University, Taichung 40227, Taiwan.
authors.forename: Ya-Chen
authors.initials: YC
authors.lastname: Liang
authors.affiliation: Institute of Molecular Biology, National Chung Hsing University, Taichung 40227, Taiwan.
authors.forename: Chia-Chin
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, Asia University, Taichung 41354, Taiwan.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Yao
authors.affiliation: Institute of Molecular Biology, National Chung Hsing University, Taichung 40227, Taiwan.
authors.forename: Chien-Chen
authors.initials: CC
authors.lastname: Lai
authors.affiliation: Institute of Biochemistry, Medical Faculty, Friedrichstrasse 24, Justus-Liebig-University, 35392 Giessen, Germany.
authors.forename: M Lienhard
authors.initials: ML
authors.lastname: Schmitz
authors.affiliation: Institute of Molecular Biology, National Chung Hsing University, Taichung 40227, Taiwan.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D008239:Lysine / Q000378:metabolism*; D061986:MCF-7 Cells; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D000071156:Promyelocytic Leukemia Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D014157:Transcription Factors / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms; C114070:RNF4 protein, human; C117909:SUMO2 protein, human; C492189:SUMO3 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D014452:Ubiquitins; C070576:PML protein, human; D008239:Lysine