GP78-2 Activators

Chemical activators of GP78-2 (gene name AMFR) include a range of compounds that influence protein folding and degradation pathways. These activators induce stress responses or inhibit processes that could lead to an increase in the functional demand for GP78-2's E3 ubiquitin ligase activity within the ERAD pathway. MG132, a proteasome inhibitor, causes accumulation of ubiquitinated proteins, which could signal for enhanced recruitment of GP78-2's ubiquitination function. Similarly, Tunicamycin and Thapsigargin disrupt protein folding within the ER, leading to ER stress and potentially upregulated GP78-2 activity to address the increased load of misfolded proteins.

Brefeldin A, DTT, and Chloroquine all induce ER stress through different mechanisms, such as inhibiting protein transport, disrupting disulfide bond formation, and altering intracellular pH, respectively. This stress can trigger an adaptive response, wherein GP78-2 activity is increased to manage the misfolded protein burden. Hsp90 inhibitors like 17-AAG and Radicicol, and the ERAD inhibitor Eeyarestatin I, might indirectly necessitate heightened GP78-2 action due to an increase in misfolded or unfolded proteins. Ubiquitin Aldehyde, by inhibiting deubiquitinating enzymes, could bolster the ubiquitin-proteasome system, where GP78-2 plays a vital role. MLN4924 and ALLN disrupt protein degradation via different targets, potentially enhancing the demand for GP78-2's role in the ubiquitination of proteins destined for degradation.