RAD6B Loss Disrupts Expression of Melanoma Phenotype in Part by Inhibiting WNT/β-Catenin Signaling.

ABSTRACT: Canonical Wnt signaling is critical for melanocyte lineage commitment and melanoma development. RAD6B, a ubiquitin-conjugating enzyme critical for translesion DNA synthesis, potentiates β-catenin stability/activity by inducing proteasome-insensitive polyubiquitination. RAD6B expression is induced by β-catenin, triggering a positive feedback loop between the two proteins. RAD6B function in melanoma development/progression was investigated by targeting RAD6B using CrispR/Cas9 or an RAD6-selective small-molecule inhibitor #9 (SMI#9). SMI#9 treatment inhibited melanoma cell proliferation but not normal melanocytes. RAD6B knockout or inhibition in metastatic melanoma cells downregulated β-catenin, β-catenin-regulated microphthalmia-associated transcription factor (MITF), sex-determining region

SUBMITTER: Sarma A 

PROVIDER: S-EPMC7888193 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature