Convergence of the SUMO and MAPK pathways on the ETS-domain transcription factor Elk-1.
The ETS-domain transcription factor Elk-1 is regulated by phosphorylation in response to activation of the MAPK (mitogen-activated protein kinase) pathways. This phosphorylation triggers a series of molecular events that convert Elk-1 from a transcriptionally silent state into a highly active state and then back to a basal level. At the same time, activation of the ERK (extracellular-signal-regulated kinase) MAPK pathway leads to loss of modification of Elk-1 by SUMO (small ubiquitin-related modifier). As SUMO imparts repressive properties on Elk-1, ERK-mediated SUMO loss leads to de-repression at the same time as the ERK pathway promotes activation of Elk-1. Thus a two-step mechanism is employed to convert Elk-1 into its fully activated state. Here, the molecular events underlying these changes in Elk-1 status, and the role of PIASxalpha [protein inhibitor of activated STAT (signal transducer and activator of transcription) xalpha] as a co-activator that facilitates this process, are discussed.
Yang
Shen-Hsi
SH
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Sharrocks
Andrew D
AD
D000818:Animals; D020935:MAP Kinase Signaling System; D051379:Mice; D008954:Models, Biological; D015394:Molecular Structure; D010766:Phosphorylation; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D017434:Protein Structure, Tertiary; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D015533:Transcriptional Activation; D050807:ets-Domain Protein Elk-1 / Q000737:chemistry / Q000378:metabolism*
D050828:Protein Inhibitors of Activated STAT; D025841:Small Ubiquitin-Related Modifier Proteins; D050807:ets-Domain Protein Elk-1