Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase.

The EMBO journal | Jun 3, 2002

http://www.ncbi.nlm.nih.gov/pubmed/12032081

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.

Pubmed ID: 12032081 RIS Download

Mesh terms: Animals | Blotting, Western | COS Cells | Cell Nucleus | Chromatin | Cytoplasm | Dimerization | Electrophoresis, Polyacrylamide Gel | Genes, Reporter | Glutathione Transferase | HeLa Cells | Histone Deacetylases | Humans | Lysine | Microscopy, Fluorescence | Molecular Chaperones | Mutation | Nuclear Pore Complex Proteins | Plasmids | Precipitin Tests | Protein Binding | Protein Structure, Tertiary | Repressor Proteins | Signal Transduction | Transcription, Genetic | Transfection