A PAX3/BRN2 rheostat controls the dynamics of BRAF mediated MITF regulation in MITF^high /AXL^low melanoma.

ABSTRACT: The BRAF kinase and the MAPK pathway are targets of current melanoma therapies. However, MAPK pathway inhibition results in dynamic changes of downstream targets that can counteract inhibitor-action not only in during treatment, but also in acquired resistant tumours. One such dynamic change involves the expression of the transcription factor MITF, a crucial regulator of cell survival and proliferation in untreated as well as drug-addicted acquired resistant melanoma. Tight control over MITF expression levels is required for optimal melanoma growth, and while it is well established that the MAPK pathway regulates MITF expression, the actual mechanism is insufficiently understood. We reveal here, how BRAF through action on the transcription factors BRN2 and PAX3 executes control over the re

SUBMITTER: Smith MP 

PROVIDER: S-EPMC6392120 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature