Lead antibacterial compound against a novel target in Gram-negative bacteria validated in infection modelsProgressing a platform of small-molecule...

Genome-wide CRISPR/Cas9 screening identifies the N-terminal acetyltransferase NAA60 to facilitate cis- and carboplatin drug sensitivity, most likely by neutralizing Nt acetylation of the LRRC8A/D VRAC subunits regulating substrate permeability.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

Degrons allow E3 ubiquitin ligases to identify their substrates, and thus have a central role in protein degradation by the ubiquitin–proteasome system. This Review discusses the latest insights into ...

Abstract. Acylamino acid-releasing enzyme (AARE) is an evolutionary deeply conserved bifunctional serine protease. In its exopeptidase mode, AARE cleaves N

N-terminal acetylation dysregulation in the heart causes severe arrhythmia and cardiomyopathy. The authors show that stem cell models demonstrate ion channel trafficking defects and sarcomeric disarra...

Co-translational N-terminal modifications such as methionine excision, acetylation, and myristoylation contribute to protein stability, localization, and folding (1). Disrupting these modifications ex...

MYC is a master regulatory transcription factor whose sustained dysregulation promotes the initiation and maintenance of numerous cancers. While MYC is a regarded as a potenial therapeutic target in cancer, its intrinsically disordered structure has proven to be a formidable barrier toward the development of highly effective small molecule inhibitors. We rationalized that proteolysis targeting chimeras (PROTACs), which might accomplish the targeted degradation of MYC, would achieve more potent cell killing in MYC-driven cancer cells than reversible inhibitors. PROTACs are bifunctional small molecules designed to produce a ternary complex between a target protein and an E3 ligase leading the target’s ubiquitination and degradation by the 26S proteasome. We generated PROTAC MTP3 based on modifications of the previously reported MYC-targeting compound KJ-Pyr-9. We found that MTP3 depletes endogenous full-length MYC proteins and uniquely induces increasing levels of a functional, N-terminally truncated MYC species, tMYC. Furthermore, MTP3 perturbs cellular MYC levels in favor of a tMYC-dominated state whose gene regulatory landscape is not significantly altered compared to that of wild type MYC. Moreover, although it lacks ∼10 kDa of MYC’s N-terminal transactivation domain, tMYC is sufficient to maintain an oncogenic proliferative state. Our results highlight the complexities of proximity-inducing compounds against highly regulated and conformationally dynamic protein targets such as MYC and indicate that PROTACs can induce alternative outcomes beyond target protein degradation.

Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic dataset...

Ubiquitin chains determine the fates of their modified proteins, including proteasomal degradation. Kiss et al. present UbiREAD, a technology to monitor cellular degradation and deubiquitination at hi...

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Acetylation is an increasing area of focus for cancer research as it is closely related to a variety of cellular processes through modulation of histone and non-histone proteins. However, broadly targ...

Informasjon om bruk av antibiotika Nasjonalt senter for antibiotikabruk i sykehus (NSAS) har som hovedoppgave å støtte norske sykehus i arbeidet med riktig bruk av antibiotika. Antibiotikasenteret for...

War appears to have accelerated the spread of pathogens resistant to antibiotics in the country.

Maintenance of proteostasis is key during aging, but the mechanisms underlying this process remain unclear. Here the authors show that the E2 enzyme UBE2D/eff, levels of which decline with skeletal mu...

N-terminal acetylation is a ubiquitous protein modification in eukaryotes. Here, the authors review the N-terminal acetylation machinery, its impact on protein function and fate, and its role in physi...