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

Area of Science:

• Cellular Biology
• Molecular Biology
• Stress Response Mechanisms

Background:

• Cellular homeostasis is crucial for organismal health, with reactive oxygen species (ROS) posing a significant threat.
• Oxidative stress, induced by ROS, disrupts cellular redox balance and can lead to pathophysiological conditions.
• The yeast activator protein-1 (YAP1) is a key transcription factor involved in oxidative detoxification, accumulating in the nucleus under stress.

Purpose of the Study:

• To identify novel genes involved in the regulation of YAP1 expression during oxidative stress.
• To investigate the role of NCE102, CDA2, and BCS1 in yeast's response to hydrogen peroxide (H2O2)-induced oxidative stress.
• To elucidate the translational mechanisms by which these genes influence YAP1 expression under stress conditions.

Main Methods:

• Generation and analysis of deletion mutant strains for candidate genes (NCE102, CDA2, BCS1).
• Assessment of H2O2 sensitivity in mutant strains.
• Investigation of YAP1 gene expression at the translational level under oxidative stress conditions.

Main Results:

• Deletion mutants of NCE102, CDA2, and BCS1 exhibited increased sensitivity to H2O2.
• These genes were found to influence YAP1 expression specifically at the level of translation.
• NCE102, CDA2, and BCS1 were shown to facilitate cap-independent translation of YAP1 under oxidative stress.

Conclusions:

• NCE102, CDA2, and BCS1 play previously unrecognized roles in managing oxidative stress in yeast.
• These genes are critical for the cap-independent translation of YAP1, a key antioxidant regulator.
• Understanding these mechanisms provides insights into cellular defense strategies against oxidative damage.