Transcription Factor Elk-1 Participates in the interleukin-1β-dependent Regulation of Expression of Immediate Early Response Gene 3 (IER3)

Cytokine. 2014 Dec;70(2):120-5. doi: 10.1016/j.cyto.2014.06.021. Epub 2014 Jul 22.

Abstract

Immediate early response gene 3 (IER3) encodes a protein involved in the regulation of apoptosis and differentiation. Recently the role of IER3 in the regulation of extracellular signal-regulated kinases (ERKs) was discovered. IER3 prolongs ERKs activation by inhibition of phosphatase PP2A. Here we show that interleukin-1β (IL-1β)-induced IER3 expression is mediated by the ERK1/2 target, transcription factor Elk-1. We identified sequences in the IER3 promoter responsible for its ERKs-dependent activation, namely ETS5/6. Elk-1 binds to these sequences and is phosphorylated following IL-1β stimulation. Mutation of ETS5/6 binding site abolishes activation of IER3 promoter by IL-1β as well as by the constitutively active form of Elk-1 (Elk-VP16). Thus IER3 acts not only as a regulator of ERKs activation, but also as a ERKs-Elk-1-dependent downstream effector.

Keywords: ERK1/2; Elk-1; IER3; IEX; Interleukin-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Base Sequence
  • Binding Sites
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics*
  • Hep G2 Cells
  • Humans
  • Interleukin-1beta / pharmacology*
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Molecular Sequence Data
  • Promoter Regions, Genetic / genetics
  • Protein Binding / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • ets-Domain Protein Elk-1 / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • IER3 protein, human
  • Interleukin-1beta
  • Membrane Proteins
  • RNA, Messenger
  • ets-Domain Protein Elk-1
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase Kinases