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USP46 increases the amount of mutated NRAS. 4 / 4
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"We found that the knockdown of USP46 in SK-MEL-103, SK-MEL-30 and SK-MEL-2 cells significantly decreased the protein level of NRAS mutants (Fig. 4a and Supplementary Fig. 4a)."
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"In addition, the overexpression of USP46 WT in SK-MEL-103 and SK-MEL-30 cells significantly increased the protein level of NRAS mutants, which could be largely mitigated by the treatment of PF670462 (Fig. 7c and Supplementary Fig. 10a)."
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"As shown in Fig. 7j and Supplementary Fig. 10g, the overexpression of USP46 WT, but not the 3 A mutant in SK-MEL-103, SK-MEL-30 and SK-MEL-2 cells significantly increased the protein level of NRAS mutants and levels of p-AKT and p-ERK."
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"Compared to control cells (shScramble), the depletion of USP46 in SK-MEL-103 cells expressing FLAG-NRAS Q61R markedly decreased the protein level of the NRAS mutant, inhibited the activation of downstream pathways assessed by p-AKT and p-ERK, reduced cell proliferation, and increased cellular sensitivity to DTIC."
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