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Recent structural progress on prokaryotic and eukaryotic Argonaute proteins is reviewed here, along with the insights obtained into guide and target binding and target cleavage. Comprehensive phylogenetic analyses lead to a map of Argonaute's evolutionary paths, relating structural features and physiological roles.
Ubiquitin E3 ligases catalyze the final step of the ubiquitination cascade, promoting the transfer of ubiquitin from the E2 to the substrate target. Recent structural and biochemical studies have given insights in the catalytic mechanisms of all three E3 ligase classes, as discussed in this Review.
Ubiquitin and ubiquitin-like (UBL) modifications occur primarily on lysine residues of target proteins to stimulate downstream signals. This Review discusses current knowledge of lysine specificity in ubiquitin and UBL targeting, with particular focus on the systems in which a detailed mechanism of modification and downstream signaling has been validated biochemically.
DNA metabolism is regulated by the ubiquitin and SUMO modifications, but DNA also influences whether and when these modifications occur. This Review describes the mutual interactions between DNA, ubiquitin and SUMO that occur in DNA-associated processes.
Whereas the proteasome degrades individual proteins modified with ubiquitin chains, autophagy degrades many proteins and organelles en masse. A pair of ubiquitin-like proteins (UBLs), Atg8 and Atg12, regulate autophagy-mediated degradation in a manner completely distinct from that of ubiquitin in the proteasome pathway, as discussed in this Review.
The endoplasmic reticulum–associated degradation (ERAD) pathway maintains protein homeostasis in the ER by retrotranslocating unwanted proteins to the cytosol for proteasomal degradation. This Review discusses the integral role of the ubiquitin system in ERAD, highlighting how the two pathways intertwine to facilitate transport across the ER membrane.
Enhancers are cis-regulatory elements that enable precise spatiotemporal patterns of gene expression during development and are notable for their ability to function at large distances from their target genes. This Review discusses classic enhancer studies, placing these in the context of recent studies that confirm the role of enhancers in orchestrating gene expression during development and their significance in disease pathogenesis.
Differences in the sex-chromosome karyotype of many animal species create imbalances between X-chromosome and autosomal gene products that require compensation. Genome-wide analyses have been instrumental in driving recent progress in understanding the transcriptional regulatory mechanisms underlying dosage compensation. This Review focuses on emerging models for dosage compensation in mammals, flies and nematodes.
