The Toll-like receptor gene family is integrated into human DNA damage and p53 networks.

In recent years the functions that the p53 tumor suppressor plays in human biology have been greatly extended beyond "guardian of the genome." Our studies of promoter response element sequences targeted by the p53 master regulatory transcription factor suggest a general role for this DNA d...

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Autores principales:	Daniel Menendez, Maria Shatz, Kathleen Azzam, Stavros Garantziotis, Michael B Fessler, Michael A Resnick
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/1c851161da124fd6ab494edb49d4b45a
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spelling	oai:doaj.org-article:1c851161da124fd6ab494edb49d4b45a2021-11-18T06:17:36ZThe Toll-like receptor gene family is integrated into human DNA damage and p53 networks.1553-73901553-740410.1371/journal.pgen.1001360https://doaj.org/article/1c851161da124fd6ab494edb49d4b45a2011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21483755/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404In recent years the functions that the p53 tumor suppressor plays in human biology have been greatly extended beyond "guardian of the genome." Our studies of promoter response element sequences targeted by the p53 master regulatory transcription factor suggest a general role for this DNA damage and stress-responsive regulator in the control of human Toll-like receptor (TLR) gene expression. The TLR gene family mediates innate immunity to a wide variety of pathogenic threats through recognition of conserved pathogen-associated molecular motifs. Using primary human immune cells, we have examined expression of the entire TLR gene family following exposure to anti-cancer agents that induce the p53 network. Expression of all TLR genes, TLR1 to TLR10, in blood lymphocytes and alveolar macrophages from healthy volunteers can be induced by DNA metabolic stressors. However, there is considerable inter-individual variability. Most of the TLR genes respond to p53 via canonical as well as noncanonical promoter binding sites. Importantly, the integration of the TLR gene family into the p53 network is unique to primates, a recurrent theme raised for other gene families in our previous studies. Furthermore, a polymorphism in a TLR8 response element provides the first human example of a p53 target sequence specifically responsible for endogenous gene induction. These findings-demonstrating that the human innate immune system, including downstream induction of cytokines, can be modulated by DNA metabolic stress-have many implications for health and disease, as well as for understanding the evolution of damage and p53 responsive networks.Daniel MenendezMaria ShatzKathleen AzzamStavros GarantziotisMichael B FesslerMichael A ResnickPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 7, Iss 3, p e1001360 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Daniel Menendez Maria Shatz Kathleen Azzam Stavros Garantziotis Michael B Fessler Michael A Resnick The Toll-like receptor gene family is integrated into human DNA damage and p53 networks.
description	In recent years the functions that the p53 tumor suppressor plays in human biology have been greatly extended beyond "guardian of the genome." Our studies of promoter response element sequences targeted by the p53 master regulatory transcription factor suggest a general role for this DNA damage and stress-responsive regulator in the control of human Toll-like receptor (TLR) gene expression. The TLR gene family mediates innate immunity to a wide variety of pathogenic threats through recognition of conserved pathogen-associated molecular motifs. Using primary human immune cells, we have examined expression of the entire TLR gene family following exposure to anti-cancer agents that induce the p53 network. Expression of all TLR genes, TLR1 to TLR10, in blood lymphocytes and alveolar macrophages from healthy volunteers can be induced by DNA metabolic stressors. However, there is considerable inter-individual variability. Most of the TLR genes respond to p53 via canonical as well as noncanonical promoter binding sites. Importantly, the integration of the TLR gene family into the p53 network is unique to primates, a recurrent theme raised for other gene families in our previous studies. Furthermore, a polymorphism in a TLR8 response element provides the first human example of a p53 target sequence specifically responsible for endogenous gene induction. These findings-demonstrating that the human innate immune system, including downstream induction of cytokines, can be modulated by DNA metabolic stress-have many implications for health and disease, as well as for understanding the evolution of damage and p53 responsive networks.
format	article
author	Daniel Menendez Maria Shatz Kathleen Azzam Stavros Garantziotis Michael B Fessler Michael A Resnick
author_facet	Daniel Menendez Maria Shatz Kathleen Azzam Stavros Garantziotis Michael B Fessler Michael A Resnick
author_sort	Daniel Menendez
title	The Toll-like receptor gene family is integrated into human DNA damage and p53 networks.
title_short	The Toll-like receptor gene family is integrated into human DNA damage and p53 networks.
title_full	The Toll-like receptor gene family is integrated into human DNA damage and p53 networks.
title_fullStr	The Toll-like receptor gene family is integrated into human DNA damage and p53 networks.
title_full_unstemmed	The Toll-like receptor gene family is integrated into human DNA damage and p53 networks.
title_sort	toll-like receptor gene family is integrated into human dna damage and p53 networks.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/1c851161da124fd6ab494edb49d4b45a
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The Toll-like receptor gene family is integrated into human DNA damage and p53 networks.

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