ZAKα Recognizes Stalled Ribosomes through Partially Redundant Sensor Domains

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

ZAKα Recognizes Stalled Ribosomes through Partially Redundant Sensor Domains. / Vind, Anna Constance; Snieckute, Goda; Blasius, Melanie; Tiedje, Christopher; Krogh, Nicolai; Bekker-Jensen, Dorte Breinholdt; Andersen, Kasper Langebjerg; Nordgaard, Cathrine; Tollenaere, Maxim Alexander Xavier; Lund, Anders Henrik; Olsen, Jesper Velgaard; Nielsen, Henrik; Bekker-Jensen, Simon.

In: Molecular Cell, Vol. 78, No. 4, 2020, p. 700-713.E7.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Vind, AC, Snieckute, G, Blasius, M, Tiedje, C, Krogh, N, Bekker-Jensen, DB, Andersen, KL, Nordgaard, C, Tollenaere, MAX, Lund, AH, Olsen, JV, Nielsen, H & Bekker-Jensen, S 2020, 'ZAKα Recognizes Stalled Ribosomes through Partially Redundant Sensor Domains', Molecular Cell, vol. 78, no. 4, pp. 700-713.E7. https://doi.org/10.1016/j.molcel.2020.03.021

APA

Vind, A. C., Snieckute, G., Blasius, M., Tiedje, C., Krogh, N., Bekker-Jensen, D. B., Andersen, K. L., Nordgaard, C., Tollenaere, M. A. X., Lund, A. H., Olsen, J. V., Nielsen, H., & Bekker-Jensen, S. (2020). ZAKα Recognizes Stalled Ribosomes through Partially Redundant Sensor Domains. Molecular Cell, 78(4), 700-713.E7. https://doi.org/10.1016/j.molcel.2020.03.021

Vancouver

Vind AC, Snieckute G, Blasius M, Tiedje C, Krogh N, Bekker-Jensen DB et al. ZAKα Recognizes Stalled Ribosomes through Partially Redundant Sensor Domains. Molecular Cell. 2020;78(4):700-713.E7. https://doi.org/10.1016/j.molcel.2020.03.021

Author

Vind, Anna Constance ; Snieckute, Goda ; Blasius, Melanie ; Tiedje, Christopher ; Krogh, Nicolai ; Bekker-Jensen, Dorte Breinholdt ; Andersen, Kasper Langebjerg ; Nordgaard, Cathrine ; Tollenaere, Maxim Alexander Xavier ; Lund, Anders Henrik ; Olsen, Jesper Velgaard ; Nielsen, Henrik ; Bekker-Jensen, Simon. / ZAKα Recognizes Stalled Ribosomes through Partially Redundant Sensor Domains. In: Molecular Cell. 2020 ; Vol. 78, No. 4. pp. 700-713.E7.

Bibtex

@article{7259ccf41d234ce38ecaad0f58192210,
title = "ZAKα Recognizes Stalled Ribosomes through Partially Redundant Sensor Domains",
abstract = "Impairment of ribosome function activates the MAPKKK ZAK, leading to activation of mitogen-activated protein (MAP) kinases p38 and JNK and inflammatory signaling. The mechanistic basis for activation of this ribotoxic stress response (RSR) remains completely obscure. We show that the long isoform of ZAK (ZAKα) directly associates with ribosomes by inserting its flexible C terminus into the ribosomal intersubunit space. Here, ZAKα binds helix 14 of 18S ribosomal RNA (rRNA). An adjacent domain in ZAKα also probes the ribosome, and together, these sensor domains are critically required for RSR activation after inhibition of both the E-site, the peptidyl transferase center (PTC), and ribotoxin action. Finally, we show that ablation of the RSR response leads to organismal phenotypes and decreased lifespan in the nematode Caenorhabditis elegans (C. elegans). Our findings yield mechanistic insight into how cells detect ribotoxic stress and provide experimental in vivo evidence for its physiological importance.",
author = "Vind, {Anna Constance} and Goda Snieckute and Melanie Blasius and Christopher Tiedje and Nicolai Krogh and Bekker-Jensen, {Dorte Breinholdt} and Andersen, {Kasper Langebjerg} and Cathrine Nordgaard and Tollenaere, {Maxim Alexander Xavier} and Lund, {Anders Henrik} and Olsen, {Jesper Velgaard} and Henrik Nielsen and Simon Bekker-Jensen",
note = "Copyright {\textcopyright} 2020 Elsevier Inc. All rights reserved.",
year = "2020",
doi = "10.1016/j.molcel.2020.03.021",
language = "English",
volume = "78",
pages = "700--713.E7",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - ZAKα Recognizes Stalled Ribosomes through Partially Redundant Sensor Domains

AU - Vind, Anna Constance

AU - Snieckute, Goda

AU - Blasius, Melanie

AU - Tiedje, Christopher

AU - Krogh, Nicolai

AU - Bekker-Jensen, Dorte Breinholdt

AU - Andersen, Kasper Langebjerg

AU - Nordgaard, Cathrine

AU - Tollenaere, Maxim Alexander Xavier

AU - Lund, Anders Henrik

AU - Olsen, Jesper Velgaard

AU - Nielsen, Henrik

AU - Bekker-Jensen, Simon

N1 - Copyright © 2020 Elsevier Inc. All rights reserved.

PY - 2020

Y1 - 2020

N2 - Impairment of ribosome function activates the MAPKKK ZAK, leading to activation of mitogen-activated protein (MAP) kinases p38 and JNK and inflammatory signaling. The mechanistic basis for activation of this ribotoxic stress response (RSR) remains completely obscure. We show that the long isoform of ZAK (ZAKα) directly associates with ribosomes by inserting its flexible C terminus into the ribosomal intersubunit space. Here, ZAKα binds helix 14 of 18S ribosomal RNA (rRNA). An adjacent domain in ZAKα also probes the ribosome, and together, these sensor domains are critically required for RSR activation after inhibition of both the E-site, the peptidyl transferase center (PTC), and ribotoxin action. Finally, we show that ablation of the RSR response leads to organismal phenotypes and decreased lifespan in the nematode Caenorhabditis elegans (C. elegans). Our findings yield mechanistic insight into how cells detect ribotoxic stress and provide experimental in vivo evidence for its physiological importance.

AB - Impairment of ribosome function activates the MAPKKK ZAK, leading to activation of mitogen-activated protein (MAP) kinases p38 and JNK and inflammatory signaling. The mechanistic basis for activation of this ribotoxic stress response (RSR) remains completely obscure. We show that the long isoform of ZAK (ZAKα) directly associates with ribosomes by inserting its flexible C terminus into the ribosomal intersubunit space. Here, ZAKα binds helix 14 of 18S ribosomal RNA (rRNA). An adjacent domain in ZAKα also probes the ribosome, and together, these sensor domains are critically required for RSR activation after inhibition of both the E-site, the peptidyl transferase center (PTC), and ribotoxin action. Finally, we show that ablation of the RSR response leads to organismal phenotypes and decreased lifespan in the nematode Caenorhabditis elegans (C. elegans). Our findings yield mechanistic insight into how cells detect ribotoxic stress and provide experimental in vivo evidence for its physiological importance.

U2 - 10.1016/j.molcel.2020.03.021

DO - 10.1016/j.molcel.2020.03.021

M3 - Journal article

C2 - 32289254

VL - 78

SP - 700-713.E7

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 4

ER -

ID: 239573724