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Stress-Free Evolution: The Nrf-Coordinated Oxidative Stress Response in Early Diverging Metazoans

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Stress-Free Evolution : The Nrf-Coordinated Oxidative Stress Response in Early Diverging Metazoans. / Doonan, Liam B.; Hartigan, Ashlie; Okamura, Beth; Long, Paul F.

In: INTEGRATIVE AND COMPARATIVE BIOLOGY, Vol. 59, No. 4, 01.10.2019, p. 799-810.

Research output: Contribution to journalArticle

Harvard

Doonan, LB, Hartigan, A, Okamura, B & Long, PF 2019, 'Stress-Free Evolution: The Nrf-Coordinated Oxidative Stress Response in Early Diverging Metazoans', INTEGRATIVE AND COMPARATIVE BIOLOGY, vol. 59, no. 4, pp. 799-810. https://doi.org/10.1093/icb/icz055

APA

Doonan, L. B., Hartigan, A., Okamura, B., & Long, P. F. (2019). Stress-Free Evolution: The Nrf-Coordinated Oxidative Stress Response in Early Diverging Metazoans. INTEGRATIVE AND COMPARATIVE BIOLOGY, 59(4), 799-810. https://doi.org/10.1093/icb/icz055

Vancouver

Doonan LB, Hartigan A, Okamura B, Long PF. Stress-Free Evolution: The Nrf-Coordinated Oxidative Stress Response in Early Diverging Metazoans. INTEGRATIVE AND COMPARATIVE BIOLOGY. 2019 Oct 1;59(4):799-810. https://doi.org/10.1093/icb/icz055

Author

Doonan, Liam B. ; Hartigan, Ashlie ; Okamura, Beth ; Long, Paul F. / Stress-Free Evolution : The Nrf-Coordinated Oxidative Stress Response in Early Diverging Metazoans. In: INTEGRATIVE AND COMPARATIVE BIOLOGY. 2019 ; Vol. 59, No. 4. pp. 799-810.

Bibtex Download

@article{a64b11f51ff844a5ab2ed2471b2a6bb3,
title = "Stress-Free Evolution: The Nrf-Coordinated Oxidative Stress Response in Early Diverging Metazoans",
abstract = "Environmental stress from ultraviolet radiation, elevated temperatures or metal toxicity can lead to reactive oxygen species in cells, leading to oxidative DNA damage, premature aging, neurodegenerative diseases, and cancer. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activates many cytoprotective proteins within the nucleus to maintain homeostasis during oxidative stress. In vertebrates, Nrf2 levels are regulated by the Kelch-family protein Keap1 (Kelch-like ECH-associated protein 1) in the absence of stress according to a canonical redox control pathway. Little, however, is known about the redox control pathway used in early diverging metazoans. Our study examines the presence of known oxidative stress regulatory elements within non-bilaterian metazoans including free living and parasitic cnidarians, ctenophores, placozoans, and sponges. Cnidarians, with their pivotal position as the sister phylum to bilaterians, play an important role in understanding the evolutionary history of response to oxidative stress. Through comparative genomic and transcriptomic analysis our results show that Nrf homologs evolved early in metazoans, whereas Keap1 appeared later in the last common ancestor of cnidarians and bilaterians. However, key Nrf-Keap1 interacting domains are not conserved within the cnidarian lineage, suggesting this important pathway evolved with the radiation of bilaterians. Several known downstream Nrf targets are present in cnidarians suggesting that cnidarian Nrf plays an important role in oxidative stress response even in the absence of Keap1. Comparative analyses of key oxidative stress sensing and response proteins in early diverging metazoans thus provide important insights into the molecular basis of how these lineages interact with their environment and suggest a shared evolutionary history of regulatory pathways. Exploration of these pathways may prove important for the study of cancer therapeutics and broader research in oxidative stress, senescence, and the functional responses of early diverging metazoans to environmental change.",
author = "Doonan, {Liam B.} and Ashlie Hartigan and Beth Okamura and Long, {Paul F.}",
year = "2019",
month = "10",
day = "1",
doi = "10.1093/icb/icz055",
language = "English",
volume = "59",
pages = "799--810",
journal = "INTEGRATIVE AND COMPARATIVE BIOLOGY",
issn = "1450-7063",
publisher = "Oxford University Press",
number = "4",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Stress-Free Evolution

T2 - The Nrf-Coordinated Oxidative Stress Response in Early Diverging Metazoans

AU - Doonan, Liam B.

AU - Hartigan, Ashlie

AU - Okamura, Beth

AU - Long, Paul F.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Environmental stress from ultraviolet radiation, elevated temperatures or metal toxicity can lead to reactive oxygen species in cells, leading to oxidative DNA damage, premature aging, neurodegenerative diseases, and cancer. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activates many cytoprotective proteins within the nucleus to maintain homeostasis during oxidative stress. In vertebrates, Nrf2 levels are regulated by the Kelch-family protein Keap1 (Kelch-like ECH-associated protein 1) in the absence of stress according to a canonical redox control pathway. Little, however, is known about the redox control pathway used in early diverging metazoans. Our study examines the presence of known oxidative stress regulatory elements within non-bilaterian metazoans including free living and parasitic cnidarians, ctenophores, placozoans, and sponges. Cnidarians, with their pivotal position as the sister phylum to bilaterians, play an important role in understanding the evolutionary history of response to oxidative stress. Through comparative genomic and transcriptomic analysis our results show that Nrf homologs evolved early in metazoans, whereas Keap1 appeared later in the last common ancestor of cnidarians and bilaterians. However, key Nrf-Keap1 interacting domains are not conserved within the cnidarian lineage, suggesting this important pathway evolved with the radiation of bilaterians. Several known downstream Nrf targets are present in cnidarians suggesting that cnidarian Nrf plays an important role in oxidative stress response even in the absence of Keap1. Comparative analyses of key oxidative stress sensing and response proteins in early diverging metazoans thus provide important insights into the molecular basis of how these lineages interact with their environment and suggest a shared evolutionary history of regulatory pathways. Exploration of these pathways may prove important for the study of cancer therapeutics and broader research in oxidative stress, senescence, and the functional responses of early diverging metazoans to environmental change.

AB - Environmental stress from ultraviolet radiation, elevated temperatures or metal toxicity can lead to reactive oxygen species in cells, leading to oxidative DNA damage, premature aging, neurodegenerative diseases, and cancer. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activates many cytoprotective proteins within the nucleus to maintain homeostasis during oxidative stress. In vertebrates, Nrf2 levels are regulated by the Kelch-family protein Keap1 (Kelch-like ECH-associated protein 1) in the absence of stress according to a canonical redox control pathway. Little, however, is known about the redox control pathway used in early diverging metazoans. Our study examines the presence of known oxidative stress regulatory elements within non-bilaterian metazoans including free living and parasitic cnidarians, ctenophores, placozoans, and sponges. Cnidarians, with their pivotal position as the sister phylum to bilaterians, play an important role in understanding the evolutionary history of response to oxidative stress. Through comparative genomic and transcriptomic analysis our results show that Nrf homologs evolved early in metazoans, whereas Keap1 appeared later in the last common ancestor of cnidarians and bilaterians. However, key Nrf-Keap1 interacting domains are not conserved within the cnidarian lineage, suggesting this important pathway evolved with the radiation of bilaterians. Several known downstream Nrf targets are present in cnidarians suggesting that cnidarian Nrf plays an important role in oxidative stress response even in the absence of Keap1. Comparative analyses of key oxidative stress sensing and response proteins in early diverging metazoans thus provide important insights into the molecular basis of how these lineages interact with their environment and suggest a shared evolutionary history of regulatory pathways. Exploration of these pathways may prove important for the study of cancer therapeutics and broader research in oxidative stress, senescence, and the functional responses of early diverging metazoans to environmental change.

UR - http://www.scopus.com/inward/record.url?scp=85073577473&partnerID=8YFLogxK

U2 - 10.1093/icb/icz055

DO - 10.1093/icb/icz055

M3 - Article

C2 - 31120488

AN - SCOPUS:85073577473

VL - 59

SP - 799

EP - 810

JO - INTEGRATIVE AND COMPARATIVE BIOLOGY

JF - INTEGRATIVE AND COMPARATIVE BIOLOGY

SN - 1450-7063

IS - 4

ER -

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