BRAF/MAPK and GSK3 signaling converges to control MITF nuclear export
Ngeow KC., Friedrichsen HJ., Li L., Zeng Z., Andrews S., Volpon L., Brunsdon H., Berridge G., Picaud S., Fischer R., Lisle R., Knapp S., Filippakopoulos P., Knowles H., Steingrímsson E., Borden KLB., Patton EE., Goding CR.
Significance Signaling pathways ultimately exert their influence on cell behavior by regulating the activity of transcription factors that drive gene expression programs associated with specific cell phenotypes. How transcription factors integrate the outputs from multiple independent signaling events to coordinate cell behavior is a key issue. Here, we identify a regulated nuclear export signal in the lineage survival oncogene and cell fate-determining factor MITF. The regulated export signal integrates the outputs from the MAPK signaling pathway with those regulating GSK3 that play key roles in development and disease. The regulation of MITF nuclear export provides a means by which these key signaling pathways tune MITF activity that, in turn, controls cell identity in development and disease.