Dynamic interplay of the SUMO and ERK pathways in regulating Elk-1 transcriptional activity

Mol Cell. 2003 Jul;12(1):63-74. doi: 10.1016/s1097-2765(03)00265-x.


The ETS domain transcription factor Elk-1 is a direct target of the MAP kinase pathways. Phosphorylation of the Elk-1 transcriptional activation domain by MAP kinases triggers its activation. However, Elk-1 also contains two domains with repressive activities. One of these, the R motif, appears to function by suppressing the activity of the activation domain. Here, we demonstrate that SUMO modification of the R motif is required for this repressive activity. A dynamic interplay exists between the activating ERK MAP kinase pathway and the repressive SUMO pathway. ERK pathway activation leads to both phosphorylation of Elk-1 and loss of SUMO conjugation and, hence, to the loss of the repressive activity of the R motif. Thus, the reciprocal regulation of the activation and repressive activities are coupled by MAP kinase modification of Elk-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DNA-Binding Proteins*
  • Eukaryotic Cells / enzymology*
  • Genes, Regulator / genetics
  • Humans
  • Mitogen-Activated Protein Kinases / genetics*
  • Mitogen-Activated Protein Kinases / metabolism
  • Protein Structure, Tertiary / genetics
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • SUMO-1 Protein / genetics*
  • SUMO-1 Protein / metabolism
  • Transcription Factors*
  • Transcription, Genetic / genetics*
  • ets-Domain Protein Elk-1


  • DNA-Binding Proteins
  • ELK1 protein, human
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • SUMO-1 Protein
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • Mitogen-Activated Protein Kinases