Evidence map›Paper›PMID 33555115›Full record

ArticleEMBO molecular medicine2021

NF45/NF90-mediated rDNA transcription provides a novel target for immunosuppressant development.

Hsiang-I Tsai, Xiaobin Zeng, Longshan Liu, Shengchang Xin, Yingyi Wu, Zhanxue Xu, Huanxi Zhang, Gan Liu, Zirong Bi, Dandan Su and 8 more

Open access · goldAbstract read
In one paragraph

Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.0field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 4 institutions in 2 countries.

Hsiang-I TsaiSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen, China.ORCID 0000-0002-4233-1428
Xiaobin ZengCenter Lab of Longhua Branch and Department of Infectious Disease, Shenzhen People's Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen, China.ORCID 0000-0002-3111-9202
Longshan LiuOrgan Transplant Centerm, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Shengchang XinState Key Laboratory of Coordination Chemistry, Institute of Chemistry and Biomedical Sciences, School of Life Sciences, Nanjing University, Nanjing, China.
Yingyi WuSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen, China.
Zhanxue XuSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen, China.
Huanxi ZhangOrgan Transplant Centerm, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Gan LiuSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen, China.
Zirong BiOrgan Transplant Centerm, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Dandan SuSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen, China.
Min YangSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen, China.
Yijing TaoSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen, China.
Changxi WangOrgan Transplant Centerm, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Jing ZhaoState Key Laboratory of Coordination Chemistry, Institute of Chemistry and Biomedical Sciences, School of Life Sciences, Nanjing University, Nanjing, China.
John E ErikssonCell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.
Wenbin DengSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen, China.
Fang ChengSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen, China.
Hongbo ChenSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen, China.ORCID 0000-0002-0954-5600
Sun Yat-sen University · CNInstitute of Chemistry · CNÅbo Akademi University · FIJinan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Nuclear Factor 45 ProteinNuclear Factor 90 ProteinsAnimalsDNA, RibosomalHumansImmunosuppressive AgentsMicePromoter Regions, GeneticDNA, RibosomalImmunosuppressive AgentsNuclear Factor 45 ProteinNuclear Factor 90 ProteinsCX5461NF45/NF90NFATnucleolusorgan transplantation

Identifiers

PMID33555115
PMCPMC7933818
OpenAlexW3127545422

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.