Nature Structural & Molecular Biology, Published online: 06 August 2025; doi:10.1038/s41594-025-01639-wGao, Nardone et al. report the cryo-EM structure of human TXNL1 bound to the proteasome and reveal interactions required for the stress-induced degradation of TXNL1, an abundant protein that may regulate proteasomal activity.

Peroxisomes execute essential functions in cells, including detoxification and lipid oxidation. Despite their centrality to cell biology, the relevance of peroxisomes to aging remains understudied. We...

The noncanonical translation initiation factor eIF2A plays critical roles in diverse cellular processes, including the integrated stress response, neurodegeneration and tumorigenesis. However, the pre...

Transcription factors (TFs) regulate gene expression by binding specific DNA motifs, yet only a fraction of putative sites is occupied in vivo. Intrinsically disordered regions (IDRs) have emerged as ...

Using biochemistry, chemical biology, and cryo-EM, Maiwald et al. elucidate how TRIP12 forms K29 linkages and K29/K48-linked branched ubiquitin chains, revealing a mechanism for polyubiquitylation sha...

Single-molecule experiments show that active conformation formation controls chromatin ubiquitylation kinetics by variant PRC1.

Nature - Molecular basis of SIFI activity in the integrated stress response

The K29/K48 hetero-polyubiquitin signal has been reported to be an enhanced degradation signal, but the enzymatic mechanism of this ubiquitin chain formation is unclear. Here, the authors reveal how t...

Loss-of-function mutations in the PINK1 kinase lead to early-onset Parkinson’s disease (PD). PINK1 is activated by mitochondrial damage to phosphorylate ubiquitin and Parkin, triggering mitophagy. PIN...

Here we describe ProtacID, a flexible BioID (proximity-dependent biotinylation)-based approach to identify PROTAC-proximal proteins in living cells. ProtacID analysis of VHL- and CRBN-recruiting PROTA...

This review discusses the cellular pathways mediating Targeted Protein Degradation approaches and points to some gaps in our understanding of the biology of novel therapeutic tools such as PROTACs.

Kazi et al. report the crystal structure of the mitochondrial deubiquitinase USP, a clinical stage Parkinson’s disease drug target, in complex with a specific inhibitor. The authors delineate a framew...

Targeted protein degradation (TPD) is an emerging pharmacological modality in cancer therapy. In this Review, Hinterndorfer et al. outline the mechanistic bases of TPD and discuss the characteristics,...

Lysosomal uptake of mtDNA controls mitochondrial quality.

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...

Ubiquitin-binding shuttle proteins are important components of stress-induced biomolecular condensates in cells. Yeast Dsk2 scaffolds proteasome-containing condensates via multivalent interactions wit...

After completing my post-doctoral training at the University of Alabama, Birmingham and a brief period on the faculty there, I joined the Department o…

Disruption of mucin-domain glycoprotein expression and function in the endothelial glycocalyx are associated with ageing and Alzheimer’s disease, leading to dysregulated blood–brain barrier function.

imageimageCertain E3 ligases have been found to ubiquitylate hydroxyl groups on free NAD+ and ADP-ribose in vitro, but the in vivo occurrence of this dual post-translational modification has remained ...

Peptide macrocycles are promising therapeutics for a variety of disease indications due to their overall metabolic stability and potential to make highly selective binding interactions with targets. R...

Huang et al. identify a pathway for stress-induced 40S ribosome degradation: 40S ribosomes ubiquitylated by RNF10 are subsequently bound by the atypical kinase RIOK3, which mediates their degradation ...