title: System-wide changes to SUMO modifications in response to heat shock.
abstract: Covalent conjugation of the small ubiquitin-like modifier (SUMO) proteins to target proteins regulates many important eukaryotic cellular mechanisms. Although the molecular consequences of the conjugation of SUMO proteins are relatively well understood, little is known about the cellular signals that regulate the modification of their substrates. Here, we show that SUMO-2 and SUMO-3 are required for cells to survive heat shock. Through quantitative labeling techniques, stringent purification of SUMOylated proteins, advanced mass spectrometric technology, and novel techniques of data analysis, we quantified heat shock-induced changes in the SUMOylation state of 766 putative substrates. In response to heat shock, SUMO was polymerized into polySUMO chains and redistributed among a wide range of proteins involved in cell cycle regulation; apoptosis; the trafficking, folding, and degradation of proteins; transcription; translation; and DNA replication, recombination, and repair. This comprehensive proteomic analysis of the substrates of a ubiquitin-like modifier (Ubl) identifies a pervasive role for SUMO proteins in the biologic response to hyperthermic stress.
authors.affiliation: 1Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
authors.forename: Filip
authors.initials: F
authors.lastname: Golebiowski
authors.forename: Ivan
authors.initials: I
authors.lastname: Matic
authors.forename: Michael H
authors.initials: MH
authors.lastname: Tatham
authors.forename: Christian
authors.initials: C
authors.lastname: Cole
authors.forename: Yili
authors.initials: Y
authors.lastname: Yin
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nakamura
authors.forename: Jürgen
authors.initials: J
authors.lastname: Cox
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Barton
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Hay
mesh_terms: D001704:Biopolymers; D002470:Cell Survival; D006367:HeLa Cells; D018869:Heat-Shock Response; D006801:Humans; D020543:Proteome; D025842:SUMO-1 Protein / Q000378:metabolism*
chemical_list: D001704:Biopolymers; D020543:Proteome; D025842:SUMO-1 Protein