title: PIASxalpha differentially regulates the amplitudes of transcriptional responses following activation of the ERK and p38 MAPK pathways.
abstract: Activation of the MAP kinase pathways leads to changes in gene expression profiles through direct targeting of transcription factors and their coregulators. Here we identify PIASxalpha as a key regulator that determines the differential response of the transcription factor Elk-1 to the ERK and the stress-activated p38 MAP kinase pathways. While PIASxalpha functions as a coactivator to facilitate SUMO and HDAC-2 removal from Elk-1 in response to ERK pathway activation, PIASxalpha acts in the opposite manner to inhibit HDAC-2 and SUMO loss following stress-activated MAP kinase pathway signaling. Thus, PIASxalpha either enhances or dampens down the activation of Elk-1 target genes, depending on the pathway activated. p38 MAP kinase-mediated PIASxalpha phosphorylation allows it to switch between these two alternative modes of operation. Thus, PIASxalpha acts as a key signal integrator that permits different responses from the same transcription factor, depending on the signaling pathway that is activated.
authors.affiliation: Faculty of Life Sciences, University of Manchester, UK.
authors.forename: Shen-Hsi
authors.initials: SH
authors.lastname: Yang
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Sharrocks
mesh_terms: D000841:Anisomycin / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D050828:Protein Inhibitors of Activated STAT / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism; D014158:Transcription, Genetic; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C494112:ELK1 protein, human; C501001:PIAS2 protein, human; D050828:Protein Inhibitors of Activated STAT; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D012097:Repressor Proteins; D025842:SUMO-1 Protein; D050807:ets-Domain Protein Elk-1; D000841:Anisomycin; D048051:p38 Mitogen-Activated Protein Kinases; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases