Research ArticleCancer

Reduced abundance of the E3 ubiquitin ligase E6AP contributes to decreased expression of the INK4/ARF locus in non–small cell lung cancer

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Sci. Signal.  10 Jan 2017:
Vol. 10, Issue 461, eaaf8223
DOI: 10.1126/scisignal.aaf8223

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INK4/ARF repression in lung cancer by loss of E6AP

The abundance of the cell cycle decelerator p16INK4a, encoded at the INK4/ARF locus, is decreased in various cancers. Gamell et al. found that the absence of p16INK4a in some patients is explained by the lack of the E3 ubiquitin ligase E6AP. E6AP bound to and inhibited the activity of transcription factor E2F1; a decrease in E6AP abundance enabled E2F1-mediated expression of the cell cycle promoter CDC6, which encodes a transcriptional regulator that represses INK4/ARF expression. The findings identify a tumor-suppressive role for E6AP in lung cancer and suggest that targeting the E2F1-CDC6 pathway might slow tumor growth in some NSCLC patients.

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