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Repression of E1AF transcriptional activity by sumoylation and PIASy

Tamotsu Nishida1, Motoko Terashima, Kiyoko Fukami

  • 1Department of Human Functional Genomics, Life Science Research Center, Mie University, 1577 Kurima-machiya, Tsu 514-8507, Japan. nishida@gene.mie-u.ac.jp

Biochemical and Biophysical Research Communications
|June 26, 2007
PubMed

Insights

Ets transcription factor E1AF

Area of Science:

  • Molecular biology
  • Cancer research
  • Transcriptional regulation

Background:

  • Ets transcription factor E1AF is implicated in tumor metastasis.
  • Mechanisms controlling E1AF activity remain largely unknown.

Purpose of the Study:

  • To investigate the role of sumoylation and PIASy in regulating E1AF transcriptional activity.

Main Methods:

  • In vivo and in vitro sumoylation assays.
  • Site-directed mutagenesis of E1AF and PIASy.
  • Transcriptional activity assays.

Main Results:

  • E1AF undergoes sumoylation at four lysine residues, which negatively regulates its activity.
  • PIASy acts as a SUMO-E3 ligase, enhancing E1AF sumoylation.
  • PIASy represses E1AF activity via both sumoylation-dependent and -independent mechanisms.

Conclusions:

  • PIASy negatively regulates E1AF-mediated transcription through dual mechanisms.
  • Sumoylation is a key post-translational modification controlling E1AF function in cancer progression.

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