Research ArticleCancer

c-MYC Suppresses BIN1 to Release Poly(ADP-Ribose) Polymerase 1: A Mechanism by Which Cancer Cells Acquire Cisplatin Resistance

Sci. Signal.  29 Mar 2011:
Vol. 4, Issue 166, pp. ra19
DOI: 10.1126/scisignal.2001556

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Losing Your Inhibitions

The antineoplastic drug cisplatin binds to actively replicating DNA, eliciting DNA lesions and, eventually, apoptosis. However, overexpression of the oncoprotein c-MYC can enable cancer cells to become resistant to cisplatin’s effects. Pyndiah et al. found that the c-MYC inhibitor BIN1 sensitized cells to DNA damage through a direct interaction with and inhibition of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP1). c-MYC, when overexpressed, inhibited expression of BIN1, thereby setting up a positive feedback loop for increased c-MYC activity and promoting cancer cell resistance to DNA-damaging agents like cisplatin.