Abstract

The CMG helicase is the main replicative helicase. Circumstantial evidence suggests that interference with the function of this helicase is detrimental for cancer cells, while tolerable for normal healthy cells, pointing to the CMG helicase as an ideal novel target for cancer treatment. Previous studies identified Retinoblastoma (Rb) protein as a potent native inhibitor of the helicase activity. For the purpose of drug discovery, here we explore Rb‐derived peptides for their abilities to inhibit the CMG helicase and proliferation of cancer cells. For the first time, we showed that Rb‐derived peptides directly inhibited activity of human CMG helicase, as assessed in an in vitro helicase assay. Importantly, Rb‐derived peptides caused a substantial decrease in the proliferation of cancer cells in vitro. Our results further support the idea of targeting CMG helicase for cancer treatment and developing novel anti‐cancer therapeutic agents based on Rb‐derived peptides.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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