Novel mechanisms of MITF regulation and melanoma predisposition identified in a mouse suppressor screen.

ABSTRACT: MITF, a basic-Helix-Loop-Helix Zipper (bHLHZip) transcription factor, plays vital roles in melanocyte development and functions as an oncogene. To explore MITF regulation and its role in melanoma, we conducted a genetic screen for suppressors of the Mitf-associated pigmentation phenotype. An intragenic Mitf mutation was identified, leading to termination of MITF at the K316 SUMOylation site and loss of the C-end intrinsically disordered region (IDR). The resulting protein is more nuclear but less stable than wild-type MITF and retains DNA-binding ability. Interestingly, as a dimer, it can translocate wild-type and mutant MITF partners into the nucleus, improving its own stability and ensuring an active nuclear MITF supply. Interactions between K316 SUMOylation and S409 phosphorylation site

SUBMITTER: Vu HN 

PROVIDER: S-EPMC10541597 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature