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 and Hsing-Jien Kung ()
Additional contact information
Chia-Lin Chen: Institute of Molecular and Genomic Medicine, National Health Research Institutes
Sheng-Chieh Hsu: National Tsing-Hua University
Tan-Ya Chung: Institute of Molecular and Genomic Medicine, National Health Research Institutes
Cheng-Ying Chu: Taipei Medical University
Hung-Jung Wang: Tzu Chi University
Pei-Wen Hsiao: Academia Sinica
Shauh- Der Yeh: Taipei Medical University Hospital
David K. Ann: Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope
Yun Yen: Taipei Medical University
Hsing-Jien Kung: Institute of Molecular and Genomic Medicine, National Health Research Institutes

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-22652-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22652-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-22652-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().