Cullin–RING receptors in rare disease biology The ubiquitin–proteasome system governs selective protein turnover in all eukaryotes, and its cullin–Really Interesting New Gene (RING) ligases represent the largest class of E3 ligases. Their substrate receptors (SRs) act as the ‘specificity engines’ of degradation, yet their contribution to human genetic disease has only recently come into focus. In this review, we provide the first systematic catalogue of 267 SRs, of which 93 are now linked to germline disorders. We synthesise emerging mechanisms, from altered degron recognition to noncanonical SR functions, and highlight how patient variants illuminate pathways for diagnosis and therapy. By connecting proteostasis, rare-disease genetics, and targeted protein degradation, SRs emerge as central nodes with broad implications for precision medicine.

Cullin–RING receptors in rare disease biology

New Review in Trends in Cell Biology with @lumirare.com.
First integrative catalogue of 267 cullin-RING substrate receptors (93 linked to germline disorders) + programmatic-friendly Excel resource for the community.

www.cell.com/trends/cell-...

CHIP, VCP, and Nucleolar Gatekeepers Remodel the Nucleolus into a Stress-Responsive Proteostasis Hub The nucleolus, classically dedicated to ribosome biogenesis, also acts as a stress-responsive proteostasis hub. During heat shock, misfolded proteins accumulate in its granular component (GC), but whe...

Preprint alert! 🚨
We reveal molecular switches that enable the nucleolus to reorganise into a proteostasis hub - coordinating protein quality control with ribosome biogenesis and cross-talk with other stress-responsive organelles.
A big tour de force by the team 💪
www.biorxiv.org/content/10.1...

We have an open postdoc position! Join us to study how ubiquitin ligases and non-canonical modifications regulate protein stability.
🗓️Apply by: 10.03.2025
🔬Start: 01.08.2025 | Warsaw
💰Salary: ~8300 PLN gross
More & apply: tinyurl.com/pokrzywalab-...
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IIMCB

We're hiring! 🚨 Looking for a talented MSc graduate to join our team to work on bacteriophages, and bacterial translation using cutting-edge techniques like transcriptomics, proteomics, and single-molecule microscopy. Apply today: bit.ly/3PQjR46

We have identified a novel MAPK1 variant linked to a unique psychiatric disorder with early-onset dementia and demonstrated its role in age-dependent neurodegeneration. Thanks to all collaborators involved!
www.researchsquare.com/article/rs-5...

DEGRADATOR: A Gaming Expedition Into Targeted Protein Degradation Therapies In an era of rapid scientific advancement, the need for engaging educational tools is critical. DEGRADATOR, a 2D computer game, bridges this gap by immersing players in the ubiquitin-proteasome system...

Our first educational project, DEGRADATOR, is now in the Journal of Chemical Education @acspublications.bsky.social
Tested with 97 high school students, it enhances understanding of protein degradation. A step towards making molecular biology more accessible.
Read more: pubs.acs.org/doi/10.1021/...