@article{deeb98adba6146cfb4e06bf070e56d32,
title = "NF45/NF90-mediated rDNA transcription provides a novel target for immunosuppressant development",
abstract = "Herein, we demonstrate that NFAT, a key regulator of the immune response, translocates from cytoplasm to nucleolus and interacts with NF45/NF90 complex to collaboratively promote rDNA transcription via triggering the directly binding of NF45/NF90 to the ARRE2-like sequences in rDNA promoter upon T-cell activation in vitro. The elevated pre-rRNA level of T cells is also observed in both mouse heart or skin transplantation models and in kidney transplanted patients. Importantly, T-cell activation can be significantly suppressed by inhibiting NF45/NF90-dependent rDNA transcription. Amazingly, CX5461, a rDNA transcription-specific inhibitor, outperformed FK506, the most commonly used immunosuppressant, both in terms of potency and off-target activity (i.e., toxicity), as demonstrated by a series of skin and heart allograft models. Collectively, this reveals NF45/NF90-mediated rDNA transcription as a novel signaling pathway essential for T-cell activation and as a new target for the development of safe and effective immunosuppressants.",
keywords = "CX5461, NF45/NF90, NFAT, nucleolus, organ transplantation",
author = "Tsai, {Hsiang i.} and Xiaobin Zeng and Longshan Liu and Shengchang Xin and Yingyi Wu and Zhanxue Xu and Huanxi Zhang and Gan Liu and Zirong Bi and Dandan Su and Min Yang and Yijing Tao and Changxi Wang and Jing Zhao and Eriksson, {John E.} and Wenbin Deng and Fang Cheng and Hongbo Chen",
note = "Funding Information: This research was supported by the National Natural Science Foundation of China (81702750, 81670141, 81970145, 81700655 and 82001698); Natural Science Foundation of Guangdong Province (2020A1515011465 and 2020A151501467); Science, Technology & Innovation Commission of Shenzhen Municipality (JCYJ20170818164756460, JCYJ20180307154700308, JCYJ20170818163844015, JCYJ20180307151420045, and JCYJ20190807151609464); Sun Yat‐sen University (20ykzd17 and 20ykpy122); International Collaboration of Science and Technology of Guangdong Province (2020A0505100031); China Postdoctoral Science Foundation (2018M643299). Publisher Copyright: {\textcopyright} 2021 The Authors. Published under the terms of the CC BY 4.0 license",
year = "2021",
month = mar,
day = "5",
doi = "10.15252/emmm.202012834",
language = "English",
volume = "13",
journal = "EMBO Molecular Medicine",
issn = "1757-4676",
publisher = "EMBO Press",
number = "3",
}