A Unified Approach to Targeting the Lysosome's Degradative and Growth Signaling Roles

针对溶酶体的降解和生长信号传导作用的统一方法

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作者:Vito W Rebecca, Michael C Nicastri, Noel McLaughlin, Colin Fennelly, Quentin McAfee, Amruta Ronghe, Michel Nofal, Chun-Yan Lim, Eric Witze, Cynthia I Chude, Gao Zhang, Gretchen M Alicea, Shengfu Piao, Sengottuvelan Murugan, Rani Ojha, Samuel M Levi, Zhi Wei, Julie S Barber-Rotenberg, Maureen E Murph

Significance

This study identifies chemical features of dimeric compounds that increase their lysosomal specificity, and a new molecular target for these compounds, reclassifying these compounds as targeted therapies. Targeting PPT1 blocks mTOR signaling in a manner distinct from catalytic inhibitors, while concurrently inhibiting autophagy, thereby providing a new strategy for cancer therapy. Cancer Discov; 7(11); 1266-83. ©2017 AACR.See related commentary by Towers and Thorburn, p. 1218This article is highlighted in the In This Issue feature, p. 1201.

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