The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase

• Verfasst von: Kirsh, Olivier [VerfasserIn]
• Verfasst von: Seeler, Jacob-S. [VerfasserIn]
• Verfasst von: Pichler, Andrea [VerfasserIn]
• Verfasst von: Gast, Andreas [VerfasserIn]
• Verfasst von: Müller, Stefan [VerfasserIn]
• Verfasst von: Miska, Eric [VerfasserIn]
• Verfasst von: Mathieu, Marion [VerfasserIn]
• Verfasst von: Harel-Bellan, Annick [VerfasserIn]
• Verfasst von: Kouzarides, Tony [VerfasserIn]
• Verfasst von: Melchior, Frauke [VerfasserIn]
• Verfasst von: Dejean, Anne [VerfasserIn]
• Titel: The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase
• Verf.angabe: Olivier Kirsh, Jacob-S. Seeler, Andrea Pichler, Andreas Gast, Stefan Müller, Eric Miska, Marion Mathieu, Annick Harel-Bellan, Tony Kouzarides, Frauke Melchior and Anne Dejean
• E-Jahr: 2002
• Jahr: 3 June 2002
• Umfang: 10 S.
• Fussnoten: Gesehen am 05.09.2023
• Titel Quelle: Enthalten in: European Molecular Biology OrganizationThe EMBO journal
• Ort Quelle: [London] : Nature Publishing Group UK, 1982
• Jahr Quelle: 2002
• Band/Heft Quelle: 21(2002), 11, Seite 2682-2691
• ISSN Quelle: 1460-2075
• DOI: doi:10.1093/emboj/21.11.2682
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: E3 ligase
• Sach-SW: HDACs
• Sach-SW: nuclear pore complex
• Sach-SW: SUMO
• Sach-SW: ubiquitin-like modification
• K10plus-PPN: 185879045X

Abstract

Transcriptional repression mediated through histone deacetylation is a critical component of eukaryotic gene regulation. Here we demonstrate that the class II histone deacetylase HDAC4 is covalently modified by the ubiquitin-related SUMO-1 modifier. A sumoylation-deficient point mutant (HDAC4-K559R) shows a slightly impaired ability to repress transcription as well as reduced histone deacetylase activity. The ability of HDAC4 to self-aggregate is a prerequisite for proper sumoylation in vivo. Calcium/calmodulin-dependent protein kinase (CaMK) signalling, which induces nuclear export, abrogates SUMO-1 modification of HDAC4. Moreover, the modification depends on the presence of an intact nuclear localization signal and is catalysed by the nuclear pore complex (NPC) RanBP2 protein, a factor newly identified as a SUMO E3 ligase. These findings suggest that sumoylation of HDAC4 takes place at the NPC and is coupled to its nuclear import. Finally, modification experiments indicate that the MEF2-interacting transcription repressor (MITR) as well as HDAC1 and -6 are similarly SUMO modified, indicating that sumoylation may be an important regulatory mechanism for the control of transcriptional repression mediated by both class I and II HDACs.