Dynamic Interplay of the SUMO and ERK Pathways in Regulating Elk-1 Transcriptional Activity

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 f...

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Bibliographic Details
Published in:Molecular cell 2003-07, Vol.12 (1), p.63-74
Main Authors: Yang, Shen-Hsi, Jaffray, Ellis, Hay, Ron T., Sharrocks, Andrew D.
Format: Article
Language:English
Subjects:
Animals
Cell Line
DNA-Binding Proteins
ets-Domain Protein Elk-1
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
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Summary: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.
ISSN:1097-2765
1097-4164
DOI:10.1016/S1097-2765(03)00265-X