The ubiquitin-proteasome pathway (UPP) and autophagy play integral roles in cellular homeostasis. As part of their normal life cycle, most proteins undergo ubiquitination for some form of redistribution, localization and/or functional modulation. However, ubiquitination is also important to the UPP and several autophagic processes. The UPP is initiated after specific lysine residues of short-lived, damaged or misfolded proteins are conjugated to ubiquitin, which targets these proteins to proteasomes. Autophagy is the endosomal/lysosomal-dependent degradation of organelles, invading microbes, zymogen granules and macromolecules such as protein, carbohydrates and lipids. Autophagy can be broadly separated into three distinct subtypes termed microautophagy, chaperone-mediated autophagy and macroautophagy. Although autophagy was once thought of as non-selective bulk degradation, advancements in the field have led to the discovery of several selective forms of autophagy. Here, we focus on the mechanisms of primary and selective mammalian autophagy pathways and highlight the current knowledge gaps in these molecular pathways.
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Cover Image
Cover Image
In this issue, Witus and colleagues (pp. 3467–3483) discuss the Ub ligase function of BRCA1/BARD1, highlighting experimental approaches, mechanistic considerations, and reagents that are useful in the study of substrate ubiquitylation. The review also looks at the current understanding of two well established BRCA1/BARD1 substrates and several recently discovered substrates. The cover image shows that BRCA1 and BARD1 bind the nucleosome substrate and E2 simultaneously. Image courtesy of Rachel E. Klevit.
Molecular mechanisms of mammalian autophagy
Charles B. Trelford, Gianni M. Di Guglielmo; Molecular mechanisms of mammalian autophagy. Biochem J 30 September 2021; 478 (18): 3395–3421. doi: https://doi.org/10.1042/BCJ20210314
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