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 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.
Yang
Shen-Hsi
SH
School of Biological Sciences, University of Manchester, 2.205 Stopford building, Oxford Road, Manchester M13 9PT, United Kingdom.
Jaffray
Ellis
E
Hay
Ron T
RT
Sharrocks
Andrew D
AD
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins; D005057:Eukaryotic Cells / Q000201:enzymology*; D005809:Genes, Regulator / Q000235:genetics; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D025842:SUMO-1 Protein / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000235:genetics*; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D025842:SUMO-1 Protein; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D020928:Mitogen-Activated Protein Kinases