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The autophagic ubiquitin‐like protein LC3 functions through interactions with LC3‐interaction regions (LIRs) of other autophagy proteins, including autophagy receptors, which stands out as a promising protein–protein interaction (PPI) target for the intervention of autophagy. Post‐translational modifications like acetylation of Lys49 on the LIR‐interacting surface could disrupt the interaction, offering an opportunity to design covalent small molecules interfering with the interface. Through screening covalent compounds, we discovered a small molecule modulator of LC3A/B that covalently modifies LC3A/B protein at Lys49. Activity‐based protein profiling (ABPP) based evaluations reveal that a derivative molecule DC‐LC3in‐D5 exhibits a potent covalent reactivity and selectivity to LC3A/B in HeLa cells. DC‐LC3in‐D5 compromises LC3B lipidation in vitro and in HeLa cells, leading to deficiency in the formation of autophagic structures and autophagic substrate degradation. DC‐LC3in‐D5 could serve as a powerful tool for autophagy research as well as for therapeutic interventions. [ABSTRACT FROM AUTHOR]

The tumor protein p53‐inducible nuclear protein 2 (TP53INP2) has been reported to participate in autophagy by interacting with autophagosome‐localized autophagy‐related protein 8 (Atg8) family proteins, including LC3. Here, we uncover a novel function for TP53INP2 in the autophagic degradation of proteins. We identify the ubiquitin‐interacting motif (UIM) of TP53INP2 that mediates its binding to ubiquitin and ubiquitinated proteins. TP53INP2 lacking the UIM is able to displace autophagic adaptor p62 from LC3, which leads to accumulation of ubiquitinated proteins in cells. Furthermore, overexpression of TP53INP2 lacking the UIM sensitizes cells to chloroquine treatment. Our findings indicate that TP53INP2 may act as a novel autophagic adaptor through recruiting ubquitinated substrates to autophagosomes for degradation. [ABSTRACT FROM AUTHOR]

High Loading Efficiency and Controlled Release of Bioactive Immunotherapeutic Proteins Using Vaterite Nanoparticles (Part. Keywords: controlled release; layer by layer technology; therapeutic proteins delivery; vaterite EN controlled release layer by layer technology therapeutic proteins delivery vaterite 1 1 1 07/21/21 20210701 NES 210701 In article 2100012, Dähne and co-workers provide a framework for the development of a vaterite-based drug delivery system as a carrier for bioactive protein-based cancer therapeutics. Controlled release, layer by layer technology, therapeutic proteins delivery, vaterite. [Extracted from the article]