id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-300418-s4wt5gim	Bedford, Lynn	Ubiquitin-like protein conjugation and the ubiquitin–proteasome system as drug targets	2010-12-10		.txt	text/plain	13080	640	37	In this Review, we first provide an overview of the enzyme classes in the UPS and UBL pathways that represent potential therapeutic targets, highlighting considerations that are important for drug discovery and recent progress in the development of small-molecule inhibitors. Studies using NF-κB-dependent human cancer models have demonstrated increased levels of the CRL1β TRCP substrate pIκBα and inhibition of NF-κB activity and apoptosis 116, 117 , suggesting the feasibility of NAE inhibition for the treatment of disease that is associated with constitutively active NF-κB signalling 112 The recent discovery of the importance of linear ubiquitin chains in NF-κB activation extends the complexity of the regulation of the system. As expected, ubiquitin-dependent processes, including the degradation of ubiquitylated proteins by the 26S proteasome, by autophagy and in the endosome-lysosome pathway, have central roles in neuronal development, homeostasis and disease.	./cache/cord-300418-s4wt5gim.txt	./txt/cord-300418-s4wt5gim.txt