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: | , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
3 June 2002
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| 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 |
| 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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