ERp27 アクチベーター

Chemical activators of ERp27 can initiate a cascade of cellular responses that lead to the functional activation of this protein, which is crucial for maintaining proper protein folding and endoplasmic reticulum (ER) function. Thapsigargin, a potent inhibitor of the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA), raises cytosolic calcium levels, which in turn can lead to ERp27 activation as part of calcium-dependent signaling pathways. Similarly, cyclopiazonic acid, also an inhibitor of SERCA, disrupts calcium homeostasis and induces ER stress, prompting the activation of ERp27. Tunicamycin blocks N-linked glycosylation, a critical process in protein maturation, leading to the unfolded protein response (UPR) and subsequent activation of ERp27 to aid in protein folding. Brefeldin A disrupts protein transport between the ER and Golgi apparatus, triggering ER stress and the UPR, which involves ERp27 in attempts to restore ER functions.

Moreover, compounds like 4-Phenylbutyric acid act as chemical chaperones to mitigate protein misfolding, consequently activating ERp27 as part of the ER-associated degradation pathway (ERAD). MG132, a proteasome inhibitor, causes the accumulation of misfolded proteins, which also induces ER stress and the UPR, leading to the activation of ERp27. Inhibitors like salubrinal and guanabenz prevent eIF2α dephosphorylation, enhancing UPR activity and thus activating ERp27. Eeyarestatin I, which inhibits ERAD, and Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, can both induce ER stress responses, resulting in the activation of ERp27. Lastly, celastrol induces a heat shock response and chloroquine alters intracellular organelle pH, both conditions that can lead to ER stress and the activation of ERp27 as the cell works to cope with these stressors.