Arginine is an epigenetic regulator targeting TEAD4 to modulate OXPHOS in prostate cancer cells

Chia Lin Chen, Sheng Chieh Hsu, Tan Ya Chung, Cheng Ying Chu, Hung Jung Wang, Pei Wen Hsiao, Shauh Der Yeh, David K. Ann, Yun Yen, Hsing Jien Kung

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
文章編號2398
期刊Nature Communications
12
發行號1
DOIs
出版狀態已發佈 - 十二月 2021

ASJC Scopus subject areas

  • 化學 (全部)
  • 生物化學、遺傳與分子生物學 (全部)
  • 物理與天文學 (全部)

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