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SBI-0206965

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https://www.readbyqxmd.com/read/26118643/small-molecule-inhibition-of-the-autophagy-kinase-ulk1-and-identification-of-ulk1-substrates
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Daniel F Egan, Matthew G H Chun, Mitchell Vamos, Haixia Zou, Juan Rong, Chad J Miller, Hua Jane Lou, Dhanya Raveendra-Panickar, Chih-Cheng Yang, Douglas J Sheffler, Peter Teriete, John M Asara, Benjamin E Turk, Nicholas D P Cosford, Reuben J Shaw
Many tumors become addicted to autophagy for survival, suggesting inhibition of autophagy as a potential broadly applicable cancer therapy. ULK1/Atg1 is the only serine/threonine kinase in the core autophagy pathway and thus represents an excellent drug target. Despite recent advances in the understanding of ULK1 activation by nutrient deprivation, how ULK1 promotes autophagy remains poorly understood. Here, we screened degenerate peptide libraries to deduce the optimal ULK1 substrate motif and discovered 15 phosphorylation sites in core autophagy proteins that were verified as in vivo ULK1 targets...
July 16, 2015: Molecular Cell
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