granzyme N Activators

Several ER stressors elicit granzyme N activity in safeguarding proteostasis. Compounds like thapsigargin and tunicamycin deplete calcium stores or impair glycosylation respectively, triggering ER stress and accumulation of misfolded proteins. Granzyme N resolves such aberrant substrates through enhanced ER-associated degradation. Tunicamycin specifically provides incorrectly processed polypeptides for granzyme N proteolysis. Additionally, granzyme N mitigates proteome imbalances from disturbed post-translational processing induced by brefeldin A perturbations of vesicle trafficking through selective degradation of damaged Golgi-associated cargoes.

Other selected agents activate granzyme N defenses through diverse mechanisms. Oxidative generators daunorubicin and sanguinarine compromise proteostasis and stimulate compensatory granzyme N responses. Translation inhibitors puromycin, harringtonine and homoharringtonine furnish truncated or misfolded nascent peptides for granzyme N clearance. Inhibitors of degradation machinery like MG-132 and bortezomib further provide substrates recognized by granzyme N, which relieves ensuing substrate accumulation through optimized proteolysis.