The role of HSP70 on ENPP1 expression and insulin-receptor activation

Antonella Marucci, Giuseppe Miscio, Libera Padovano, Watip Boonyasrisawat, Jose C. Florez, Alessandro Doria, Vincenzo Trischitta, Rosa Di Paola

Research output: Contribution to journalArticle

Abstract

Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) inhibits insulin-receptor (IR) signaling and, when over-expressed, induces insulin resistance in vitro and in vivo. Understanding the regulation of ENPP1 expression may, thus, unravel new molecular mechanisms of insulin resistance. Recent data point to a pivotal role of the ENPP1 3'UTR, in modulating ENPP1 mRNA stability and expression. We sought to identify trans-acting proteins binding the ENPP1-3'UTR and to investigate their role on ENPP1 expression and on IR signaling. By RNA electrophoresis mobility shift analysis and tandem mass spectrometry, we demonstrated the binding of heat shock protein 70 (HSP70) to ENPP1-3'UTR. Through this binding, HSP70 stabilizes ENPP1 mRNA and increases ENPP1 transcript and protein levels. This positive modulation of ENPP1 expression is paralleled by a reduced insulin-induced IR and IRS-1 phosphorylation. Taken together these data suggest that HSP70, by affecting ENPP1 expression, may be a novel mediator of altered insulin signaling.

Original languageEnglish
Pages (from-to)139-144
Number of pages6
JournalJournal of Molecular Medicine
Volume87
Issue number2
DOIs
Publication statusPublished - Feb 2009

Keywords

  • 3 untranslated regions
  • Inhibitors of insulin signaling
  • Insulin resistance
  • Tyrosine-kinase receptors

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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