Autophagy dictates sensitivity to PRMT5 inhibitor in breast cancer

Autophagy dictates sensitivity to PRMT5 inhibitor in breast cancer

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Abstract Protein arginine methyltransferase 5 (PRMT5) catalyzes mono-methylation and symmetric di-methylation on arginine residues and has deauville shop coupons emerged as a potential antitumor target with inhibitors being tested in clinical trials.However, it remains unknown how the efficacy of PRMT5 inhibitors is regulated.Here we report that autophagy blockage enhances cellular sensitivity to PRMT5 inhibitor in triple negative breast cancer cells.

Genetic ablation or pharmacological inhibition of PRMT5 triggers cytoprotective autophagy.Mechanistically, PRMT5 catalyzes monomethylation of ULK1 at R532 to suppress ULK1 activation, leading to attenuation of autophagy.As a result, ULK1 inhibition blocks PRMT5 deficiency-induced autophagy and sensitizes cells to PRMT5 inhibitor.

Our study not only identifies autophagy as an inducible factor that dictates cellular sensitivity to PRMT5 inhibitor, but also unearths a critical molecular mechanism by which PRMT5 regulates autophagy where to buy new iphone 14 in minneapolis mn through methylating ULK1, providing a rationale for the combination of PRMT5 and autophagy inhibitors in cancer therapy.