| Literature DB >> 27300436 |
Marco Napoli1, Avinashnarayan Venkatanarayan2, Payal Raulji1, Brooke A Meyers1, William Norton3, Lingegowda S Mangala4, Anil K Sood4, Cristian Rodriguez-Aguayo5, Gabriel Lopez-Berestein5, Harina Vin6, Madeleine Duvic6, Michael B Tetzlaff7, Jonathan L Curry7, Alain H Rook8, Hussein A Abbas1, Cristian Coarfa9, Preethi H Gunaratne10, Kenneth Y Tsai11, Elsa R Flores12.
Abstract
ΔNp63 is an oncogenic member of the p53 family and acts to inhibit the tumor-suppressive activities of the p53 family. By performing a chemical library screen, we identified histone deacetylase inhibitors (HDACi) as agents reducing ΔNp63 protein stability through the E3 ubiquitin ligase, Fbw7. ΔNp63 inhibition decreases the levels of its transcriptional target, DGCR8, and the maturation of let-7d and miR-128, which we found to be critical for HDACi function in vitro and in vivo. Our work identified Fbw7 as a predictive marker for HDACi response in squamous cell carcinomas and lymphomas, and unveiled let-7d and miR-128 as specific targets to bypass tumor resistance to HDACi treatment.Entities:
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Year: 2016 PMID： 27300436 PMCID： PMC4908836 DOI： 10.1016/j.ccell.2016.04.016
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743