Figure 2.
Model of MITF regulation through ERK downstream of oncogenic BRAF. Three types of melanoma cell populations can be classified by their MITF, AXL and WNT5A status. In MITF‐positive/AXL ‐/WNT5A‐ melanoma cells, MITF expression is regulated through the ERK target BRN2. When ERK activity is high, the BRAF/BRN2 contribution to transcription from the M‐MITF promoter is high. High ERK activity also leads to an increased MITF protein turnover; as a consequence, MITF protein levels are low. The opposite applies to low ERK activity. BRAF also contributes to the post‐translational regulation of MITF via MEK and ERK, and this will impact on MITF function at any level of MITF expression. In MITF‐negative/AXL +/WNT5A+ cells, ERK activity as well as BRN2 expression can be high or low and are uncoupled from MITF expression.