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Transcription factor RFX7 governs a tumor suppressor network in response to p53 and stress

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Názov: Transcription factor RFX7 governs a tumor suppressor network in response to p53 and stress
Autori: Luis Coronel, Konstantin Riege, Katjana Schwab, Silke Förste, David Häckes, Lena Semerau, Stephan H Bernhart, Reiner Siebert, Steve Hoffmann, Martin Fischer
Zdroj: Nucleic Acids Res
Informácie o vydavateľovi: Cold Spring Harbor Laboratory, 2021.
Rok vydania: 2021
Predmety: 0301 basic medicine, 0303 health sciences, Antibiotics, Antineoplastic, Gene regulation, Chromatin and Epigenetics, Apoptosis, Cell Differentiation, Regulatory Factor X Transcription Factors, DNA, Prognosis, Signal Transduction, Cell Line, Tumor [MeSH], Neoplasms/mortality [MeSH], Tumor Suppressor Protein p53/metabolism [MeSH], Genes, Tumor Suppressor [MeSH], Stress, Physiological/genetics [MeSH], Apoptosis [MeSH], Mice, Cell Differentiation/genetics, Antibiotics, Antineoplastic/pharmacology [MeSH], Promoter Regions, Genetic, Doxorubicin/pharmacology [MeSH], Transcriptome, Regulatory Factor X Transcription Factors/metabolism, Tumor Suppressor Protein p53/metabolism, Regulatory Factor X Transcription Factors/physiology [MeSH], Gene Expression Regulation [MeSH], DNA/metabolism [MeSH], Regulatory Factor X Transcription Factors/physiology, Trans-Activators/metabolism, Humans, Antibiotics, Antineoplastic/pharmacology, Cell Line, Tumor, Gene Expression Regulation, Doxorubicin/pharmacology, Neoplasms/genetics, Regulatory Factor X Transcription Factors/metabolism [MeSH], Humans [MeSH], Cell Differentiation/genetics [MeSH], DNA/metabolism, Neoplasms/genetics [MeSH], Animals [MeSH], Stress, Physiological/genetics, Mice [MeSH], Gene Regulatory Networks [MeSH], Prognosis [MeSH], Signal Transduction [MeSH], Transcriptome [MeSH], Animals, Neoplasms/mortality, Genes, Tumor Suppressor, Trans-Activators/metabolism [MeSH], Gene Regulatory Networks, Promoter Regions, Genetic [MeSH], 03 medical and health sciences, Doxorubicin, Stress, Physiological, Neoplasms, Trans-Activators
Popis: Despite its prominence, the mechanisms through which the tumor suppressor p53 regulates most genes remain unclear. Recently, the regulatory factor X 7 (RFX7) emerged as a suppressor of lymphoid neoplasms, but its regulation and target genes mediating tumor suppression remain unknown. Here, we identify a novel p53-RFX7 signaling axis. Integrative analysis of the RFX7 DNA binding landscape and the RFX7-regulated transcriptome in three distinct cell systems reveals that RFX7 directly controls multiple established tumor suppressors, including PDCD4, PIK3IP1, MXD4, and PNRC1, across cell types and is the missing link for their activation in response to p53 and stress. RFX7 target gene expression correlates with cell differentiation and better prognosis in numerous cancer types. Interestingly, we find that RFX7 sensitizes cells to Doxorubicin by promoting apoptosis. Together, our work establishes RFX7’s role as a ubiquitous regulator of cell growth and fate determination and a key node in the p53 transcriptional program.
Druh dokumentu: Article
Conference object
Other literature type
ISSN: 1362-4962
0305-1048
DOI: 10.1101/2021.03.25.436917
DOI: 10.1093/nar/gkab575
Prístupová URL adresa: https://www.biorxiv.org/content/biorxiv/early/2021/03/25/2021.03.25.436917.full.pdf
https://academic.oup.com/nar/article-pdf/49/13/7437/39117219/gkab575.pdf
https://pubmed.ncbi.nlm.nih.gov/34197623
https://pubmed.ncbi.nlm.nih.gov/34197623/
https://europepmc.org/article/PPR/PPR303396
https://oparu.uni-ulm.de/xmlui/handle/123456789/39060
https://academic.oup.com/nar/article/49/13/7437/6312752
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287911
https://www.biorxiv.org/content/biorxiv/early/2021/03/25/2021.03.25.436917.full.pdf
https://www.biorxiv.org/content/10.1101/2021.03.25.436917v1
https://repository.publisso.de/resource/frl:6432870
Rights: CC BY NC
URL: http://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (http://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Prístupové číslo: edsair.doi.dedup.....1c23ccaea6fe28945d0112e62d31e221
Databáza: OpenAIRE
Popis
Abstrakt:Despite its prominence, the mechanisms through which the tumor suppressor p53 regulates most genes remain unclear. Recently, the regulatory factor X 7 (RFX7) emerged as a suppressor of lymphoid neoplasms, but its regulation and target genes mediating tumor suppression remain unknown. Here, we identify a novel p53-RFX7 signaling axis. Integrative analysis of the RFX7 DNA binding landscape and the RFX7-regulated transcriptome in three distinct cell systems reveals that RFX7 directly controls multiple established tumor suppressors, including PDCD4, PIK3IP1, MXD4, and PNRC1, across cell types and is the missing link for their activation in response to p53 and stress. RFX7 target gene expression correlates with cell differentiation and better prognosis in numerous cancer types. Interestingly, we find that RFX7 sensitizes cells to Doxorubicin by promoting apoptosis. Together, our work establishes RFX7’s role as a ubiquitous regulator of cell growth and fate determination and a key node in the p53 transcriptional program.
ISSN:13624962
03051048
DOI:10.1101/2021.03.25.436917