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The central role of G protein-coupled receptors (GPCRs) in most aspects of biological signal transduction has made them the object of extensive studies for a long period of time. These studies have revealed the key physiological roles of the many members of this family, and the manifold functions they have in the central nervous system (CNS) and the periphery (for recent reviews, see refs. [1,2])...
The NEDD8-activating enzyme (NAE) initiates a protein homeostatic pathway essential for cancer cell growth and survival. MLN4924 is a selective inhibitor of NAE currently in clinical trials for the treatment of cancer. Here, we show that MLN4924 is a mechanism-based inhibitor of NAE and creates a covalent NEDD8-MLN4924 adduct catalyzed by the enzyme. The NEDD8-MLN4924 adduct resembles NEDD8 adenylate,...
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