A. Ciulli

Design of a Cereblon construct for crystallographic and biophysical studies of protein degraders

The paper introduces CRBNmidi, a Cereblon construct that enables high-resolution structural and biophysical studies of degraders without requiring DDB1 co-expression.

Combination of AID2 and BromoTag expands the utility of degron-based protein knockdowns

The paper combines AID2 and BromoTag degron systems to enhance protein depletion, demonstrating their effectiveness in suppressing DNA replication by co-depleting ORC1 and CDC6.

Confounding factors in targeted degradation of short-lived proteins

This study shows that the natural half-life of a target protein significantly affects degradation by degrader agents and highlights confounding factors in screening for protein degraders.

Mechanism of degrader-targeted protein ubiquitinability

The paper solves cryo-EM structures of a degrader-mediated complex to reveal structural insights into target protein ubiquitination mechanisms.

Targeting cancer with small molecule pan-KRAS degraders

A single small molecule degrader targets 13 out of 17 prevalent oncogenic KRAS alleles, inhibiting growth of KRAS-driven cancer cell lines and inducing tumour regression in vivo.

Targeted protein degradation via intramolecular bivalent glues

This paper introduces intramolecular bivalent glues (IBGs) as a new method for targeted protein degradation, showing they enhance ubiquitination by bridging protein domains and improving degradation efficiency.

VHL inhibitor binding increases intracellular level of VHL

This study shows VHL inhibitors increase intracellular VHL levels through protein stabilization, leading to reduced HIF-1 protein and selective HIF activation.

Structural insights into substrate recognition by the SOCS2 E3 ubiquitin ligase

This study determines the structure of SOCS2 bound to phosphorylated peptides, revealing substrate recognition mechanisms and implications for ligand design.

SPR-measured dissociation kinetics of PROTAC ternary complexes influence target degradation rate

This paper develops an SPR-based assay to measure PROTAC ternary complex dissociation kinetics and shows that differences in off-rates correlate with target degradation efficiency.