Gene regulation in the immediate-early response process

Adv Biol Regul. 2016 Sep;62:37-49. doi: 10.1016/j.jbior.2016.05.001. Epub 2016 May 13.

Abstract

Immediate-early genes (IEGs) can be activated and transcribed within minutes after stimulation, without the need for de novo protein synthesis, and they are stimulated in response to both cell-extrinsic and cell-intrinsic signals. Extracellular signals are transduced from the cell surface, through receptors activating a chain of proteins in the cell, in particular extracellular-signal-regulated kinases (ERKs), mitogen-activated protein kinases (MAPKs) and members of the RhoA-actin pathway. These communicate through a signaling cascade by adding phosphate groups to neighboring proteins, and this will eventually activate and translocate TFs to the nucleus and thereby induce gene expression. The gene activation also involves proximal and distal enhancers that interact with promoters to simulate gene expression. The immediate-early genes have essential biological roles, in particular in stress response, like the immune system, and in differentiation. Therefore they also have important roles in various diseases, including cancer development. In this paper we summarize some recent advances on key aspects of the activation and regulation of immediate-early genes.

Keywords: Enhancers; Immediate-early response; Poised genes; Signaling cascades; Transcription factors.

Publication types

  • Review

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Cell Differentiation
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / genetics*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation*
  • Genes, Immediate-Early*
  • Humans
  • Mitogen-Activated Protein Kinases / genetics*
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation
  • Promoter Regions, Genetic
  • Signal Transduction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Actins
  • Transcription Factors
  • RHOA protein, human
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinases
  • rhoA GTP-Binding Protein