Interplay of the SUMO and MAP kinase pathways.
The SUMO modification pathway has been linked with controlling the activity of numerous transcriptional regulatory proteins. In the majority of substrates studied so far, sumoylation imparts repressive properties. In several cases, part of this mechanism has been shown to be due to SUMO-dependent recruitment of histone deacetylases (HDACs). This is exemplified by the transcription factor Elk-1, where HDAC-2 is specifically recruited in response to sumoylation. Importantly, activation of the ERK MAP kinase pathway leads to Elk-1 desumoylation and HDAC loss. Furthermore, PIAS proteins can regulate the activities of transcription factors in SUMO-dependent and -independent manners. Further links between the MAP kinase pathways and PIAS proteins have been uncovered, suggesting a complex interplay been the MAP kinase and SUMO modification pathways. Here we discuss the current evidence suggesting links between the SUMO and MAP kinase pathways and point to other potential regulatory events and how these might be affected in cancer.
Faculty of Life Sciences, University of Manchester, UK.
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Yang
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Sharrocks
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism
D050828:Protein Inhibitors of Activated STAT; D012097:Repressor Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D050807:ets-Domain Protein Elk-1; D048049:Extracellular Signal-Regulated MAP Kinases; D006655:Histone Deacetylases