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SUMOylation of the transcription factor NFATc1 leads to its subnuclear relocalization and IL2 repression by HDAC

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The family of NFAT (Nuclear Factor of Activated T-cells) transcription factors plays an important role in cytokine gene regulation. In peripheral T-cells, NFATc1 and c2 are pre-dominantly expressed. Due to different promoter and polyA site usage as well as alternative splicing events, NFATc1 is synthesized in multiple isoforms. The highly inducible NF-ATc1/A contains a relatively short C-terminus whereas the longer, constitutively expressed isoform NFATc1/C spans an extra C-terminal peptide of 246 amino acids. Interestingly, this NFATc1/C-specific terminus can be highly sumoylated. Upon sumoylation, NFATc1/C – but not the unsumoylated NFATc1/A – translocates to Promyelocytic Leukemia-nuclear bodies (PML-nbs). This leads to interaction with HDACs followed by deacetylation of histones, which in turn induces transcriptionally inactive chromatin. As a consequence, expression of the NFATc1 target gene interleukin-2 is suppressed. These findings demonstrate that the modification by SUMO converts NFATc1 from an activator to a site-specific transcriptional repressor, revealing a novel regulatory mechanism for NFATc1 function.

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Correspondence to A Nayak.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Nayak, A., Glöckner-Pagel, J., Vaeth, M. et al. SUMOylation of the transcription factor NFATc1 leads to its subnuclear relocalization and IL2 repression by HDAC. Cell Commun Signal 7, A7 (2009) doi:10.1186/1478-811X-7-S1-A7

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Keywords

  • Peptide
  • Transcription Factor
  • Regulatory Mechanism
  • Alternative Splice
  • Transcriptional Repressor