Tan et al. designed a DNA-encoded library, comprising compact and diverse linkers, that recruits FKBP12 to any protein of interest to enable efficient discovery of non-degrader proximity inducers. The screen uncovered a compound that stabilized and…

Acta Pharmacologica Sinica - Nicotinamide mononucleotide protects septic hearts in mice via preventing cyclophilin F modification and lysosomal dysfunction

Bifunctional molecules such as targeted protein degraders induce proximity to promote gain-of-function pharmacology. These powerful approaches have gained broad traction across academia and the pharm....

A hallmark of neurodegenerative diseases (NDs) is the progressive loss of proteostasis, leading to the accumulation of misfolded proteins or protei...

Studies using mouse models of lung adenocarcinoma identify an association between age, iron homeostasis and tumour initiation potential that involves NUPR1 and lipocalin-2.

This work identifies reactive oxygen species released by the electron transport chain as sentinel molecules that regulate localized protein degradation at mitochondrial TOM complexes, a mechanism that controls mitochondrial protein import and adjusts the abundance of the electron transport chain to cellular needs.

Cell Death & Differentiation - USP19 potentiates autophagic cell death via inhibiting mTOR pathway through deubiquitinating NEK9 in pancreatic cancer

Targeted protein degradation (TPD) is a pharmacological strategy that eliminates specific proteins from cells by harnessing cellular proteolytic degradation machinery. In proteasome-dependent TPD, exp...

The maintenance of cholesterol homeostasis is crucial for normal function at both the cellular and organismal levels. Two integral membrane protein...

Abstract. Autophagy pathway plays a central role in cellular degradation. The proteins involved in the core autophagy process are mostly localised on membr

Harnessing autophagy for targeted degradation is a promising extension to proteasome-based targeted protein degradation because of the capacity and versatility of lysosomes to degrade large and comple...

Autophagosome tethering compounds (ATTECs) are small molecule degraders hijacking the autophagy system. Here, the authors show that current ATTEC ligands did not bind to their designated targets but e...

KEAP1 promotes persistent T cell immunity and a stem-like T cell response during chronic antigen stimulation by repressing NRF2.