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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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Main Authors: Kirsh, Olivier (Author) , Seeler, Jacob-S. (Author) , Pichler, Andrea (Author) , Gast, Andreas (Author) , Müller, Stefan (Author) , Miska, Eric (Author) , Mathieu, Marion (Author) , Harel-Bellan, Annick (Author) , Kouzarides, Tony (Author) , Melchior, Frauke (Author) , Dejean, Anne (Author)
Format: Article (Journal)
Language:English
Published: 3 June 2002
In: The EMBO journal
Year: 2002, Volume: 21, Issue: 11, Pages: 2682-2691
ISSN:1460-2075
DOI:10.1093/emboj/21.11.2682
Online Access: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
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Author Notes: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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Summary: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.
Item Description:Gesehen am 05.09.2023
Physical Description:Online Resource
ISSN:1460-2075
DOI:10.1093/emboj/21.11.2682

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