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Verfasst von:Stankovic-Valentin, Nicolas [VerfasserIn]   i
 Drzewicka, Katarzyna [VerfasserIn]   i
 König, Cornelia [VerfasserIn]   i
 Schiebel, Elmar [VerfasserIn]   i
 Melchior, Frauke [VerfasserIn]   i
Titel:Redox regulation of SUMO enzymes is required for ATM activity and survival in oxidative stress
Verf.angabe:Nicolas Stankovic-Valentin, Katarzyna Drzewicka, Cornelia König, Elmar Schiebel & Frauke Melchior
E-Jahr:2016
Jahr:12 May 2016
Umfang:18 S.
Fussnoten:Gesehen am 13.05.2020
Titel Quelle:Enthalten in: European Molecular Biology OrganizationThe EMBO journal
Ort Quelle:[London] : Nature Publishing Group UK, 1982
Jahr Quelle:2016
Band/Heft Quelle:35(2016), 12, Seite 1312-1329
ISSN Quelle:1460-2075
Abstract:Abstract To sense and defend against oxidative stress, cells depend on signal transduction cascades involving redox-sensitive proteins. We previously identified SUMO (small ubiquitin-related modifier) enzymes as downstream effectors of reactive oxygen species (ROS). Hydrogen peroxide transiently inactivates SUMO E1 and E2 enzymes by inducing a disulfide bond between their catalytic cysteines. How important their oxidation is in light of many other redox-regulated proteins has however been unclear. To selectively disrupt this redox switch, we identified a catalytically fully active SUMO E2 enzyme variant (Ubc9 D100A) with strongly reduced propensity to maintain a disulfide with the E1 enzyme in vitro and in cells. Replacement of Ubc9 by this variant impairs cell survival both under acute and mild chronic oxidative stresses. Intriguingly, Ubc9 D100A cells fail to maintain activity of the ATM?Chk2 DNA damage response pathway that is induced by hydrogen peroxide. In line with this, these cells are also more sensitive to the ROS-producing chemotherapeutic drugs etoposide/Vp16 and Ara-C. These findings reveal that SUMO E1~E2 oxidation is an essential redox switch in oxidative stress.
DOI:doi:10.15252/embj.201593404
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.15252/embj.201593404
 Volltext: https://www.embopress.org/doi/full/10.15252/embj.201593404
 DOI: https://doi.org/10.15252/embj.201593404
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:ATM
 oxidative stress
 redox regulation
 SUMO
 Ubc9
K10plus-PPN:1698135238
Verknüpfungen:→ Zeitschrift

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