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PIASy controls ubiquitination-dependent proteasomal degradation of Ets-1.

The ETS transcription factor Ets-1 (E26 transformation-specific-1) plays a critical role in many physiological processes including angiogenesis, haematopoietic development and tumour progression. Its activity can be regulated by post-translational modifications, such as phosphorylation. Recently, we showed that Ets-1 is a target for SUMO (small ubiquitin-like modifier) modification and that PIASy [protein inhibitor of activated STAT (signal transducer and activator of transcription) Y], a specific SUMO-E3 ligase for Ets-1, represses Ets-1-dependent transcription. In the present study, we demonstrated that Ets-1 is degraded by the proteasome and that overexpression of PIASy increased the stability of endogenous and ectopically expressed Ets-1 protein by preventing proteasomal degradation. Moreover, knockdown of the endogenous PIASy expression by RNA interference reduced the protein level of endogenous Ets-1. The proteasome inhibitor MG132 reversed this effect. Deletion analysis showed that the TAD (transcriptional activation domain), which has been identified as the interaction domain with PIASy, was also required for Ets-1 ubiquitination and proteasomal degradation. However, the Ets-1 stabilization by PIASy was not due to reduced ubiquitination of Ets-1. Our results suggested that PIASy controls Ets-1 function, at least in part, by inhibiting Ets-1 protein turnover via the ubiquitin-proteasome system.

Pubmed ID: 17456046

Authors

  • Nishida T
  • Terashima M
  • Fukami K
  • Yamada Y

Journal

The Biochemical journal

Publication Data

August 1, 2007

Associated Grants

None

Mesh Terms

  • Animals
  • COS Cells
  • Cell Line, Tumor
  • Cercopithecus aethiops
  • Gene Expression Regulation
  • Humans
  • Osteosarcoma
  • Proteasome Endopeptidase Complex
  • Protein Inhibitors of Activated STAT
  • Proto-Oncogene Protein c-ets-1
  • Ubiquitins