title: A new vertebrate SUMO enzyme family reveals insights into SUMO-chain assembly.
abstract: SUMO chains act as stress-induced degradation tags or repair factor-recruiting signals at DNA lesions. Although E1 activating, E2 conjugating and E3 ligating enzymes efficiently assemble SUMO chains, specific chain-elongation mechanisms are unknown. E4 elongases are specialized E3 ligases that extend a chain but are inefficient in the initial conjugation of the modifier. We identified ZNF451, a representative member of a new class of SUMO2 and SUMO3 (SUMO2/3)-specific enzymes that execute catalysis via a tandem SUMO-interaction motif (SIM) region. One SIM positions the donor SUMO while a second SIM binds SUMO on the back side of the E2 enzyme. This tandem-SIM region is sufficient to extend a back side-anchored SUMO chain (E4 elongase activity), whereas efficient chain initiation also requires a zinc-finger region to recruit the initial acceptor SUMO (E3 ligase activity). Finally, we describe four human proteins sharing E4 elongase activities and their function in stress-induced SUMO2/3 conjugation.
authors.affiliation: Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Eisenhardt
authors.affiliation: Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Viduth K
authors.initials: VK
authors.lastname: Chaugule
authors.affiliation: Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Koidl
authors.affiliation: Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Droescher
authors.affiliation: Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Esen
authors.identifier: http://orcid.org/0000-0003-0558-145X
authors.initials: E
authors.lastname: Dogan
authors.affiliation: Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rettich
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Sutinen
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
authors.forename: Susumu Y
authors.identifier: http://orcid.org/0000-0002-3641-4390
authors.initials: SY
authors.lastname: Imanishi
authors.affiliation: Institute for Genetics, University of Cologne, Cologne, Germany.
authors.forename: Kay
authors.identifier: http://orcid.org/0000-0002-2289-9083
authors.initials: K
authors.lastname: Hofmann
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jorma J
authors.initials: JJ
authors.lastname: Palvimo
authors.affiliation: Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pichler
mesh_terms: D000818:Animals; D006801:Humans; D055503:Protein Multimerization; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D014714:Vertebrates
chemical_list: D025841:Small Ubiquitin-Related Modifier Proteins