Methylarginine targeting chimeras for lysosomal degradation of intracellular proteins.

A paradigm shift in drug development is the discovery of small molecules that harness the ubiquitin-proteasomal pathway to eliminate pathogenic proteins. Here we provide a modality for targeted protein degradation in lysosomes. We exploit an endogenous lysosomal pathway whereby protein arginine methyltransferases (PRMTs) initiate substrate degradation via arginine methylation.

Vitamin B is governed by the local compartmentalization of metabolic enzymes during growth.

Vitamin B is a vital micronutrient across cell types and tissues, and dysregulated B levels contribute to human disease. Despite its importance, how B vitamer levels are regulated is not well understood. Here, we provide evidence that B dynamics are rapidly tuned by precise compartmentation of pyridoxal kinase (PDXK), the rate-limiting B enzyme.

Simplifying the B Complex: How Vitamins B6 and B9 Modulate One Carbon Metabolism in Cancer and Beyond.

Vitamin B micronutrients are essential regulators of one carbon metabolism that ensures human health. Vitamin B9, or folate, lies at the heart of the folate cycle and converges with the methionine cycle to complete the one carbon pathway. Additionally, vitamin B6 contributes by orchestrating the flux of one carbon cycling.