Proteolysis-targeting chimaeras (PROTACs) as well as molecular glues such as immunomodulatory drugs (IMiDs) and indisulam are drugs that induce interactions between substrate proteins and an E3 ubiquitin ligases for targeted protein degradation. Here, we develop a workflow based on proximity-dependent biotinylation by AirID to identify drug-induced neo-substrates of the E3 ligase cereblon (CRBN). Using AirID-CRBN, we detect IMiD-dependent biotinylation of CRBN neo-substrates in vitro and identify biotinylated peptides of well-known neo-substrates by mass spectrometry with high specificity and selectivity. Additional analyses reveal ZMYM2 and ZMYM2-FGFR1 fusion protein—responsible for the 8p11 syndrome involved in acute myeloid leukaemia—as CRBN neo-substrates. Furthermore, AirID-DCAF15 and AirID-CRBN biotinylate neo-substrates targeted by indisulam and PROTACs, respectively, suggesting that this approach has the potential to serve as a general strategy for characterizing drug-inducible protein–protein interactions in cells.
An environmentally friendly oxidative cleavage of tetrahydrofuran-2-methanols to the corresponding g-lactones using ac atalytic amount of 2-iodo-N-isopropylbenzamide hasb een developed. Ther eactiono fv arious tetrahydrofuran-2-methanols with the catalyst in the presence of Oxone (2 KHSO 5 ·KHSO 4 ·K 2 SO 4 )a saco-oxidant in DMF at room temperature successfully affords the corresponding lactones in good to high yields,a nd recovery of the catalyst is readily accomplished using areductive work-up.T his method is notable because it enables the transformation of tetrahydrofuran-2-methanols to g-lactones under mild conditions without the use of any toxicheavy metals.
Although the reliability and safety level of tasks have been improved by using operation manuals, analyses of problems recently experienced in the nuclear energy industry imply that the cause of these problems is attributable to the content and presentation of operation manuals. The importance of operation manuals has also been pointed out in relation to the Fukushima Daiichi nuclear power plant accident. Operation manuals that are eŠective for both normal and extreme conditions are desirable. The purpose of the present study is to investigate the eŠect of the manner of rule presentation on human task performance under both normal and extreme conditions. A cognitive experiment using a simulation environment has been conducted. A smart grid simulator has been adopted as an example task. Two operation manuals (manuals A and B) are prepared. Manual A describes the required operations in detail. Manual B describes the meaning of the operations with their underlying knowledge. Subjects have been divided into two groups (A Group and AB Group). Subjects in the A Group can rely on manual A. On the other hand, subjects in the AB Group can rely on both manuals A and B. Results of cognitive experiments imply that, under both normal and extreme conditions, subjects in the AB group have better performance.
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