title: Heat shock induces a massive but differential inactivation of SUMO-specific proteases.
abstract: Covalent conjugation of the small ubiquitin-like modifier (SUMO) to proteins is a highly dynamic and reversible process. Cells maintain a fine-tuned balance between SUMO conjugation and deconjugation. In response to stress stimuli such as heat shock, this balance is altered resulting in a dramatic increase in the levels of SUMO conjugates. Whether this reflects an activation of the conjugation cascade, a decrease in the activity of SUMO-specific proteases (SENPs), or both, remains unknown. Here, we show that from the five human SENPs detected in HeLa cells (SENP1/2/3/6/7) the activities of all but one (SENP6) were largely diminished after 30min of heat shock. The decreased activity is not due to changes in their steady-state levels. Rather, in vitro experiments suggest that these SENPs are intrinsically heat-sensitive, a property most likely emerging from their catalytic domains. Heat shock inactivation seems to be a specific property of SENPs because numerous members of the related deubiquitinase family of cysteine proteases are not affected by this stress condition. Overall, our results suggest that SENPs are particularly sensitive to heat shock, a property that may be important for the adaptation of cells to this stress condition.
authors.affiliation: Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal.
authors.forename: Manuel P
authors.initials: MP
authors.lastname: Pinto
authors.forename: Andreia F
authors.initials: AF
authors.lastname: Carvalho
authors.forename: Cláudia P
authors.initials: CP
authors.lastname: Grou
authors.forename: José E
authors.initials: JE
authors.lastname: Rodríguez-Borges
authors.forename: Clara
authors.initials: C
authors.lastname: Sá-Miranda
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Azevedo
mesh_terms: D020134:Catalytic Domain; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D006367:HeLa Cells; D018869:Heat-Shock Response; D006801:Humans; D058767:Protein Unfolding; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D013194:Staining and Labeling; D013379:Substrate Specificity; D013696:Temperature
chemical_list: D025841:Small Ubiquitin-Related Modifier Proteins; D003546:Cysteine Endopeptidases