UTP14B Activators

Chemical activators of UTP14B can induce stress in various cellular pathways, leading to an increased demand for ribosome biogenesis quality control, where UTP14B plays a critical role. 6-Aminonicotinamide (6-AN) is known to inhibit the pentose phosphate pathway, altering the NADP+/NADPH ratio and consequently increasing the need for ribosome biogenesis quality control mechanisms, thereby activating UTP14B. Similarly, Cycloheximide disrupts protein synthesis by blocking the translocation step, causing ribosome stalling and necessitating the involvement of UTP14B in the surveillance and rescue of defective ribosomal particles. Puromycin and Anisomycin disrupt translation by causing premature chain termination and interfering with peptide chain elongation, respectively. These actions can lead to an accumulation of defective ribosomal particles, which in turn activates UTP14B's role in ribosome-associated quality control processes. Homoharringtonine also inhibits the initiation and elongation phases of protein synthesis, potentially leading to ribosome stalling and subsequent activation of UTP14B.

Moreover, agents such as Tunicamycin, Dithiothreitol, Thapsigargin, and Brefeldin A induce different types of cellular stress, all of which can lead to an enhanced role for UTP14B in maintaining ribosome function. Tunicamycin blocks N-linked glycosylation, causing stress in the endoplasmic reticulum (ER), while Dithiothreitol disrupts disulfide bonds, causing oxidative stress and misfolded proteins. Thapsigargin disrupts calcium homeostasis by inhibiting the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase, leading to ER stress. Brefeldin A causes ER stress by disrupting ER-Golgi transport. All these stressors can activate UTP14B to address the heightened need for ribosome biogenesis quality control. Emetine and Chloramphenicol, although through different mechanisms, inhibit elongation and termination steps or block peptidyl transferase activity, respectively, leading to ribosomal stalling and further activating UTP14B's role. Lastly, MG132 impedes proteasome function, leading to an accumulation of misfolded proteins and subsequently necessitating the activation of UTP14B within the ribosome-associated quality control complex.