PIASxalpha differentially regulates the amplitudes of transcriptional responses following activation of the ERK and p38 MAPK pathways.
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.
Yang
Shen-Hsi
SH
Faculty of Life Sciences, University of Manchester, UK.
Sharrocks
Andrew D
AD
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
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