New way to control cell metabolism, growth, autophagy
Research into how protein kinase G works to suppress cardiac disease led to the discovery that it phosphorylates and in turn activates the protein TSC2, that thereby inhibits mTORC1 complex signaling. The result is reduced pathological hypertrophy and enhanced autophagy to reduce accumulation of misfolded protein aggregates and proteotoxicity. A single serine on TSC2 is involved, so genetic mutations at this one residue provide a novel method to modulate mTORC1 activation. Ongoing studies have explored its impact on other cardiac diseases, but also in other cell types and disorders. Major ongoing efforts are testing its role to improve adoptive cell therapy – such as chimeric antigen receptor (CAR)-T therapy used for immune-oncology treatment. Another effort is examining its impact in regulatory T cells to treat autoimmune disease, and still another is focusing on neurological disease such as Tuberous Sclerosis, and Alzheimer’s.