PIASxα 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 PIASx alpha as a key regulator that determines the differential response of the transcription factor EIk-1 to the ERK and the stress-activated p38 MAP kinase pathways. While PIASxoc functions as a coactivator to facilitate SUMO and HDAC-2 removal from EIk-1 in response to ERK pathway activation, PIASx alpha acts in the opposite manner to inhibit HDAC-2 and SUMO loss following stress-activated MAP kinase pathway signaling. Thus, PIASxa either enhances or dampens down the activation of EIk-1 target genes, depending on the pathway activated. p38 MAP kinase-mediated PIASx alpha phosphorylation allows it to switch between these two alternative modes of operation. Thus, PIASx alpha acts as a key signal integrator that permits different responses from the same transcription factor, depending on the signaling pathway that is activated.