@article{bf2415efdfec49f184dd1027fa8b44ac,
title = "Arginine is an epigenetic regulator targeting TEAD4 to modulate OXPHOS in prostate cancer cells",
abstract = "Arginine plays diverse roles in cellular physiology. As a semi-essential amino acid, arginine deprivation has been used to target cancers with arginine synthesis deficiency. Arginine-deprived cancer cells exhibit mitochondrial dysfunction, transcriptional reprogramming and eventual cell death. In this study, we show in prostate cancer cells that arginine acts as an epigenetic regulator to modulate histone acetylation, leading to global upregulation of nuclear-encoded oxidative phosphorylation (OXPHOS) genes. TEAD4 is retained in the nucleus by arginine, enhancing its recruitment to the promoter/enhancer regions of OXPHOS genes and mediating coordinated upregulation in a YAP1-independent but mTOR-dependent manner. Arginine also activates the expression of lysine acetyl-transferases and increases overall levels of acetylated histones and acetyl-CoA, facilitating TEAD4 recruitment. Silencing of TEAD4 suppresses OXPHOS functions and prostate cancer cell growth in vitro and in vivo. Given the strong correlation of TEAD4 expression and prostate carcinogenesis, targeting TEAD4 may be beneficially used to enhance arginine-deprivation therapy and prostate cancer therapy.",
author = "Chen, {Chia Lin} and Hsu, {Sheng Chieh} and Chung, {Tan Ya} and Chu, {Cheng Ying} and Wang, {Hung Jung} and Hsiao, {Pei Wen} and Yeh, {Shauh Der} and Ann, {David K.} and Yun Yen and Kung, {Hsing Jien}",
note = "Funding Information: We thank Core Instrument Center of NHRI for providing service for microarray analysis, seahorse assay, and real-time PCR assay and the laboratory animal center of NHRI for animal study. We also thank the CRISPR Gene Targeting Core Lab and Image Core at Taipei Medical University in Taiwan for providing technical support. This work was supported by grants MOST 106-2321-B-400-012-MY3 (to C.-L.C.) and MOST 105-2314-B-400-019-MY3, MOST 107-2320-B-038-055-MY3, MOST 105-2320-B-038-071-MY3, MOST 108-2320-B-038-011-MY3 (to H.-J.K.), as well as TMU Research Center of Cancer Translational Medicine supported by the Featured Areas Research Center Program/Higher Education Sprout Project to Y.Y. and H.-J.K. We are also grateful to Institute of Biological Sciences, National Taiwan University and Institute of Biological Chemistry, Academia Sinica for providing stimulating research environment. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41467-021-22652-9",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
