5430405G05Rik Activators

Chemical activators of transmembrane protein 74B (TMEM74B) include a variety of compounds that induce cellular stress, leading to the activation of this stress response protein. Cycloheximide, for example, acts by inhibiting protein biosynthesis, which in turn can lead to an increased expression of TMEM74B as part of the cell's compensatory mechanisms to cope with reduced protein production. Similarly, thapsigargin, by disrupting calcium homeostasis through its inhibition of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), can trigger the unfolded protein response, a cellular stress response that often involves the activation of proteins such as TMEM74B. Tunicamycin contributes to this response by blocking N-linked glycosylation, causing endoplasmic reticulum stress that can also result in the activation of TMEM74B. Furthermore, proteostasis disruptors like MG132, which inhibits the proteasome, lead to an accumulation of misfolded proteins, a condition that typically activates TMEM74B as part of the cellular attempt to restore protein homeostasis.

In addition to these, chemical activators that interfere with various cellular functions can also lead to the activation of TMEM74B. Brefeldin A, by inhibiting ER to Golgi transport, induces ER stress that may activate TMEM74B. Chloroquine, through its accumulation in lysosomes and consequent impairment of lysosomal function, can activate TMEM74B as part of the lysosomal stress response. Cellular energy stress induced by 2-Deoxy-D-glucose, which inhibits glycolysis, can similarly activate TMEM74B as the cell responds to energy deficits. Toxic stress, such as that caused by cadmium chloride, results in oxidative stress and the cellular activation of TMEM74B in response to metal-induced toxicity. Additionally, TMEM74B can be activated by redox imbalances caused by dithiothreitol, a reducing agent, or by the oxidative stress induced by hydrogen peroxide. These various chemical activators, by disrupting different cellular pathways and processes, each contribute to the activation of TMEM74B, a protein that plays a role in the cell's response to stress.