Discovery - University of Dundee - Online Publications

Library & Learning Centre

Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals

Standard

Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals. / McMahon, Michael (Lead / Corresponding author); Lamont, Douglas J.; Beattie, Kenneth A.; Hayes, John D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 44, 02.11.2010, p. 18838-18843.

Research output: Contribution to journalArticle

Harvard

McMahon, M, Lamont, DJ, Beattie, KA & Hayes, JD 2010, 'Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals' Proceedings of the National Academy of Sciences of the United States of America, vol 107, no. 44, pp. 18838-18843., 10.1073/pnas.1007387107

APA

McMahon, M., Lamont, D. J., Beattie, K. A., & Hayes, J. D. (2010). Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals. Proceedings of the National Academy of Sciences of the United States of America, 107(44), 18838-18843. 10.1073/pnas.1007387107

Vancouver

McMahon M, Lamont DJ, Beattie KA, Hayes JD. Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals. Proceedings of the National Academy of Sciences of the United States of America. 2010 Nov 2;107(44):18838-18843. Available from: 10.1073/pnas.1007387107

Author

McMahon, Michael (Lead / Corresponding author); Lamont, Douglas J.; Beattie, Kenneth A.; Hayes, John D. / Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 44, 02.11.2010, p. 18838-18843.

Research output: Contribution to journalArticle

Bibtex - Download

@article{f804f4aa06974b3889bfee1d1ed82fbc,
title = "Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals",
keywords = "TRANSCRIPTION FACTOR NRF2, OXIDATIVE STRESS, HEME OXYGENASE-1, PROTEASOMAL DEGRADATION, PHASE-2 ENZYMES, CELLULAR STRESS, INDUCTION, PROTEIN, ACTIVATION, CELLS",
author = "Michael McMahon and Lamont, {Douglas J.} and Beattie, {Kenneth A.} and Hayes, {John D.}",
year = "2010",
doi = "10.1073/pnas.1007387107",
volume = "107",
number = "44",
pages = "18838--18843",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals

A1 - McMahon,Michael

A1 - Lamont,Douglas J.

A1 - Beattie,Kenneth A.

A1 - Hayes,John D.

AU - McMahon,Michael

AU - Lamont,Douglas J.

AU - Beattie,Kenneth A.

AU - Hayes,John D.

PY - 2010/11/2

Y1 - 2010/11/2

N2 - Recognition and repair of cellular damage is crucial if organisms are to survive harmful environmental conditions. In mammals, the Keap1 protein orchestrates this response, but how it perceives adverse circumstances is not fully understood. Herein, we implicate NO, Zn(2+), and alkenals, endogenously occurring chemicals whose concentrations increase during stress, in this process. By combining molecular modeling with phylogenetic, chemical, and functional analyses, we show that Keap1 directly recognizes NO, Zn(2+), and alkenals through three distinct sensors. The C288 alkenal sensor is of ancient origin, having evolved in a common ancestor of bilaterans. The Zn(2+) sensor minimally comprises H225, C226, and C613. The most recent sensor, the NO sensor, emerged coincident with an expansion of the NOS gene family in vertebrates. It comprises a cluster of basic amino acids (H129, K131, R135, K150, and H154) that facilitate S-nitrosation of C151. Taken together, our data suggest that Keap1 is a specialized sensor that quantifies stress by monitoring the intracellular concentrations of NO, Zn(2+), and alkenals, which collectively serve as second messengers that may signify danger and/or damage.

AB - Recognition and repair of cellular damage is crucial if organisms are to survive harmful environmental conditions. In mammals, the Keap1 protein orchestrates this response, but how it perceives adverse circumstances is not fully understood. Herein, we implicate NO, Zn(2+), and alkenals, endogenously occurring chemicals whose concentrations increase during stress, in this process. By combining molecular modeling with phylogenetic, chemical, and functional analyses, we show that Keap1 directly recognizes NO, Zn(2+), and alkenals through three distinct sensors. The C288 alkenal sensor is of ancient origin, having evolved in a common ancestor of bilaterans. The Zn(2+) sensor minimally comprises H225, C226, and C613. The most recent sensor, the NO sensor, emerged coincident with an expansion of the NOS gene family in vertebrates. It comprises a cluster of basic amino acids (H129, K131, R135, K150, and H154) that facilitate S-nitrosation of C151. Taken together, our data suggest that Keap1 is a specialized sensor that quantifies stress by monitoring the intracellular concentrations of NO, Zn(2+), and alkenals, which collectively serve as second messengers that may signify danger and/or damage.

KW - TRANSCRIPTION FACTOR NRF2

KW - OXIDATIVE STRESS

KW - HEME OXYGENASE-1

KW - PROTEASOMAL DEGRADATION

KW - PHASE-2 ENZYMES

KW - CELLULAR STRESS

KW - INDUCTION

KW - PROTEIN

KW - ACTIVATION

KW - CELLS

UR - http://www.scopus.com/inward/record.url?scp=78650509515&partnerID=8YFLogxK

U2 - 10.1073/pnas.1007387107

DO - 10.1073/pnas.1007387107

M1 - Article

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 44

VL - 107

SP - 18838

EP - 18843

ER -

Documents

Library & Learning Centre

Contact | Accessibility | Policy