Coordinated sumoylation and ubiquitination modulate EGF induced EGR1 expression and stability

Daniela Tavian, Arcangela Gabriella Manente, Giulia Pinton, Gerardo Lopez-Rodas, Elisa Brunelli, Laura Moro

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

28 Citazioni (Scopus)

Abstract

Abstract: Background: Human early growth response-1 (EGR1) is a member of the zing-finger family of transcription factors induced by a range of molecular and environmental stimuli including epidermal growth factor (EGF). In a recently published paper we demonstrated that integrin/EGFR cross-talk was required for Egr1 expression through activation of the Erk1/2 and PI3K/Akt/Forkhead pathways. EGR1 activity and stability can be influenced by many different post-translational modifications such as acetylation, phosphorylation, ubiquitination and the recently discovered sumoylation. The aim of this work was to assess the influence of sumoylation on EGF induced Egr1 expression and/or stability. Methods: We modulated the expression of proteins involved in the sumoylation process in ECV304 cells by transient transfection and evaluated Egr1 expression in response to EGF treatment at mRNA and protein levels. Results: We demonstrated that in ECV304 cells Egr1 was transiently induced upon EGF treatment and a fraction of the endogenous protein was sumoylated. Moreover, SUMO-1/Ubc9 over-expression stabilized EGF induced ERK1/2 phosphorylation and increased Egr1 gene transcription. Conversely, in SUMO-1/Ubc9 transfected cells, EGR1 protein levels were strongly reduced. Data obtained from protein expression and ubiquitination analysis, in the presence of the proteasome inhibitor MG132, suggested that upon EGF stimuli EGR1 sumoylation enhanced its turnover, increasing ubiquitination and proteasome mediated degradation. Conclusions: Here we demonstrate that SUMO-1 modification improving EGR1 ubiquitination is involved in the modulation of its stability upon EGF mediated induction.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaPLoS One
Volume6
DOI
Stato di pubblicazionePubblicato - 2011

Keywords

  • Cell line
  • Early growth response
  • Mitogen-activated protein
  • enzyme activation
  • epidermal growth factor
  • gene expression regulation
  • kinase 1
  • protein 1

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