Oxidative stress‐induced YAP1 expression is regulated by NCE102, CDA2, and BCS1

Maintaining cellular homeostasis in the face of stress conditions is vital for the overall well‐being of an organism. Reactive oxygen species (ROS) are among the most potent cellular stressors and can disrupt the internal redox balance, giving rise to oxidative stress. Elevated levels of ROS can severely affect biomolecules and have been associated with a range of pathophysiological conditions. In response to oxidative stress, yeast activator protein‐1 (Yap1p) undergoes post‐translation modification that results in its nuclear accumulation. YAP1 has a key role in oxidative detoxification by promoting transcription of numerous antioxidant genes. In this study, we identified previously undescribed functions for NCE102, CDA2, and BCS1 in YAP1 expression in response to oxidative stress induced by hydrogen peroxide (H2O2). Deletion mutant strains for these candidates demonstrated increased sensitivity to H2O2. Our follow‐up investigation linked the activity of these genes to YAP1 expression at the level of translation. Under oxidative stress, global cap‐dependent translation is inhibited, prompting stress‐responsive genes like YAP1 to employ alternative modes of translation. We provide evidence that NCE102, CDA2, and BCS1 contribute to cap‐independent translation of YAP1 under oxidative stress. Under oxidative stress induced by H2O2, cap‐dependent translation is suppressed. YAP1, essential for responding to oxidative stress, undergoes IRES‐mediated translation in the presence of H2O2. NCE102, CDA2, and BCS1 may contribute to YAP1 translation through YAP1 IRES, directly or indirectly. The indirect mechanism may involve the interaction of NCE102, CDA2, and BCS1 with various factors, including specific translation initiation factors, ribosomes, or other ITAFs.