Proteolytic Activation of Fatty Acid Synthase Controls Pan-Stress Response_Datasets

However, artificially expressing FASN-CTF under stressful conditions compromises survival suggesting rather than mitigating stress, FASN-CTF is a potent signal to reduce pan-stress response programs. As cysteine proteases, catalytic activities of caspases are dependent on fully reduced cysteine. Under stressful conditions, we show that CED-3 caspase proteolytic activation decreases in vivo due to a more oxidative cellular environment.

Consequently, stressful conditions prevent FASN-CTF generation by inhibiting caspase activity, thereby allowing robust stress response with enhanced expression of UPR and innate immunity genes along with sequestration of lipids. In summary, our findings suggest that caspase cleavage of FASN to generate FASN-CTF signals a stress-free state and licenses use of energy stores thereby limiting the magnitude of responsiveness to diverse stressors.