Volume 7 Supplement 1

12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes

Open Access

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

  • A Nayak1,
  • J Glöckner-Pagel1,
  • M Vaeth1,
  • M Buttmann2,
  • T Bopp3,
  • E Schmitt3,
  • E Serfling1 and
  • F Berberich-Siebelt1
Cell Communication and Signaling20097(Suppl 1):A7

DOI: 10.1186/1478-811X-7-S1-A7

Published: 26 February 2009

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.

Authors’ Affiliations

(1)
Department of Molecular Pathology, Institute of Pathology, University of Würzburg
(2)
Department of Neurology, University of Würzburg
(3)
Institute of Immunology, University Mainz

Copyright

© Nayak et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

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