TXNDC13 Activators

TXNDC13 activators primarily include molecules that induce endoplasmic reticulum (ER) stress or disrupt protein folding, thereby indirectly increasing the demand for TXNDC13's protein disulfide isomerase activity. For instance, Thapsigargin, A23187, Brefeldin A, Monensin, and Cyclopiazonic Acid induce ER stress through various mechanisms. Thapsigargin and Cyclopiazonic Acid inhibit the SERCA pump, depleting ER calcium stores, while A23187 disrupts cellular calcium homeostasis and Monensin disrupts cellular ion gradients. Brefeldin A disrupts protein transport from the ER to the Golgi, leading to an accumulation of proteins in the ER and thus ER stress. In response to the increased load of unfolded or misfolded proteins in the ER, TXNDC13 can be activated to assist in protein folding and disulfide bond formation.

On the other hand, DTT, a reducing agent, can indirectly activate TXNDC13 by increasing the demand for disulfide bond formation and rearrangement. Tunicamycin inhibits N-linked glycosylation,leading to glycosylation defects that TXNDC13 can respond to by assisting in protein folding. In the same vein, 2-Deoxy-D-glucose can indirectly activate TXNDC13 due to increased cellular stress and consequent increase in misfolded proteins. Eeyarestatin I, which inhibits ER-associated degradation, also leads to the accumulation of misfolded proteins in the ER, indirectly activating TXNDC13.

Chemical chaperones like Sodium 4-phenylbutyrate and Tauroursodeoxycholic Acid also indirectly activate TXNDC13 by increasing the demand for protein folding assistance. Similarly, MG-132 can indirectly activate TXNDC13 by causing the accumulation of misfolded proteins.