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The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase
Author(s) -
Kirsh Olivier,
Seeler JacobS.,
Pichler Andrea,
Gast Andreas,
Müller Stefan,
Miska Eric,
Mathieu Marion,
HarelBellan Annick,
Kouzarides Tony,
Melchior Frauke,
Dejean Anne
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.11.2682
Subject(s) - sumo protein , hdac4 , histone deacetylase 5 , ubiquitin ligase , histone deacetylase , histone deacetylase 2 , microbiology and biotechnology , nuclear export signal , nuclear transport , hdac11 , chemistry , biology , histone , ubiquitin , biochemistry , cell nucleus , gene , cytoplasm
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.