PIASxα Differentially Regulates the Amplitudes of Transcriptional Responses Following Activation of the ERK and p38 MAPK Pathways

SummaryActivation of the MAP kinase pathways leads to changes in gene expression profiles through direct targeting of transcription factors and their coregulators. Here we identify PIASxα 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 PIASxα functions as a coactivator to facilitate SUMO and HDAC-2 removal from Elk-1 in response to ERK pathway activation, PIASxα acts in the opposite manner to inhibit HDAC-2 and SUMO loss following stress-activated MAP kinase pathway signaling. Thus, PIASxα either enhances or dampens down the activation of Elk-1 target genes, depending on the pathway activated. p38 MAP kinase-mediated PIASxα phosphorylation allows it to switch between these two alternative modes of operation. Thus, PIASxα acts as a key signal integrator that permits different responses from the same transcription factor, depending on the signaling pathway that is activated.