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CSNK1 phosphorylates USP46. 9 / 9
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"We next investigated whether CK1δ could phosphorylate USP46."
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"Mechanistically, CK1δ-mediated phosphorylation of USP46 is a critical post-translational mechanism that controls stability and oncogenic function of these NRAS mutants."
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"Mechanistically, CK1δ directly phosphorylates and activates USP46, thereby promoting oncogenic NRAS-driven melanocyte transformation and tumor progression."
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"CK1δ-mediated phosphorylation of USP46 in the in vitro kinase assay was detected by using phospho-tag gel, which was significantly mitigated by the treatment of PF670462 (Fig. 6d)."
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"As shown in Supplementary Fig. 9c, CK1δ significantly increased the phosphorylation of USP46 WT assessed by anti-p-Ser and anti-p-Thr antibodies, whereas the 3A mutant could largely decrease such phosphorylation events."
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"These results suggest that CK1δ directly phosphorylates USP46 and activates its deubiquitinase activity toward NRAS Q61R."
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"Next, we examined the effect of CK1δ-mediated phosphorylation of USP46 on the ubiquitination of NRAS mutants."
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"These results indicate that CK1δ stabilizes NRAS mutant in melanoma in a USP46-dependent manner.We next investigated the function of CK1δ-mediated phosphorylation of USP46 on oncogenic NRAS-dependent malignant processes."
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"These results indicate that CK1δ-mediated phosphorylation of USP46 is pivotal to stabilize NRAS mutant and promote oncogenic NRAS-dependent tumor progression."
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