The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase

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)...

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Hauptverfasser: Kirsh, Olivier (VerfasserIn) , Seeler, Jacob-S. (VerfasserIn) , Pichler, Andrea (VerfasserIn) , Gast, Andreas (VerfasserIn) , Müller, Stefan (VerfasserIn) , Miska, Eric (VerfasserIn) , Mathieu, Marion (VerfasserIn) , Harel-Bellan, Annick (VerfasserIn) , Kouzarides, Tony (VerfasserIn) , Melchior, Frauke (VerfasserIn) , Dejean, Anne (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 3 June 2002
In: The EMBO journal
Year: 2002, Jahrgang: 21, Heft: 11, Pages: 2682-2691
ISSN:1460-2075
DOI:10.1093/emboj/21.11.2682
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1093/emboj/21.11.2682
Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.1093/emboj/21.11.2682
Volltext
Verfasserangaben: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

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520 |a 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. 
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