Caspase 3 regulation of AMPK

AMP-activated protein kinase (AMPK) is a crucial metabolic enzyme that maintains cellular energy homeostasis and has been implicated in various diseases, including cancer. AMPK’s role in cancer is complicated, however recent advances have provided some clarity whereby it was shown to be proteolytically cleaved by cell death effectors called caspases. Specifically, caspase-3 cleaves AMPK, leading to its accumulation in the nucleus, where it modulates gene expression to promote cell survival. Our research has replicated some of these findings and identified additional caspase-3 cleavage sites on AMPK. We have also explored how these cleavage events influence other regulatory inputs on AMPK. These exciting discoveries provide new insights into how AMPK can promote cancer growth and resistance to chemotherapies in certain contexts, opening potential therapeutic avenues to enhance cancer treatments. This project will employ a diverse array of laboratory techniques, including biochemistry, mass spectrometry, and cell biology, providing the successful applicant with a comprehensive skill set.