Multiprotein bridging factor 1 is required for robust
activation of the integrated stress response on collided
ribosomes

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Multiprotein bridging factor 1 is required for robust activation of the integrated stress response ...

Přehled o publikaci

J 2024

Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes

KIM, Kyusik Q.; Jeffrey J. LI; Ankanahalli N. URS NANJARAJ; Miguel E. PACHECO; Victor LASEHINDE et. al.

Basic information

Original name

Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes

Authors

Edition

Molecular Cell, CAMBRIDGE, CELL PRESS, 2024, 1097-2765

Other information

Language

English

Type of outcome

Article in a journal

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Organization

Středoevropský technologický institut – Repository – Repository

DOI

http://dx.doi.org/10.1016/j.molcel.2024.10.029

UT WoS

001376472600001

EID Scopus

2-s2.0-85210612902

Keywords in English

Gcn2; Gcn4; Mbf1; integrated stress response; ribosome; ribosome collisions; translation

Links

LX22NPO5103, research and development project.

Changed: 28/1/2025 00:50, RNDr. Daniel Jakubík

Abstract

V originále

In yeast, multiprotein bridging factor 1 (Mbf1) has been proposed to function in the integrated stress response (ISR) as a transcriptional coactivator by mediating a direct interaction between general transcription machinery and the process's key effector, Gcn4. However, mounting evidence has demonstrated that Mbf1 (and its human homolog EDF1) is recruited to collided ribosomes, a known activator of the ISR. In this study, we connect these otherwise seemingly disparate functions of Mbf1. Our biochemical and structural analyses reveal that Mbf1 functions as a core ISR factor by interacting with collided ribosomes to mediate Gcn2 activation. We further show that Mbf1 serves no role as a transcriptional coactivator of Gcn4. Instead, Mbf1 is required for optimal stress-induced eukaryotic initiation factor 2alpha (eIF2alpha) phosphorylation and downstream de-repression of GCN4 translation. Collectively, our data establish that Mbf1 functions in ISR signaling by acting as a direct sensor of stress-induced ribosome collisions.

Files attached

https://is.muni.cz/publication/2455002/1-s2.0-S1097276524008694-main.pdf

https://is.muni.cz/publication/2455002/1-s2.0-S1097276524008694-main_B.pdf

Cite

KIM, Kyusik Q.; Jeffrey J. LI; Ankanahalli N. URS NANJARAJ; Miguel E. PACHECO; Victor LASEHINDE; Timo DENK; Petr TĚŠINA; Shota TOMOMATSU; Yoshitaka MATSUO; Elesa MCDONALD; Roland BECKMANN; Toshifumi INADA; Rachel GREEN and Hani S. ZAHER. Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes. Molecular Cell. CAMBRIDGE: CELL PRESS, 2024, vol. 84, No 23, p. 1-28. ISSN 1097-2765. Available from: https://dx.doi.org/10.1016/j.molcel.2024.10.029.

@article{65046,
   author = {Kim, Kyusik Q. and Li, Jeffrey J. and Urs Nanjaraj, Ankanahalli N. and Pacheco, Miguel E. and Lasehinde, Victor and Denk, Timo and Těšina, Petr and Tomomatsu, Shota and Matsuo, Yoshitaka and McDonald, Elesa and Beckmann, Roland and Inada, Toshifumi and Green, Rachel and Zaher, Hani S.},
   article_location = {CAMBRIDGE},
   article_number = {23},
   doi = {http://dx.doi.org/10.1016/j.molcel.2024.10.029},
   keywords = {Gcn2; Gcn4; Mbf1; integrated stress response; ribosome; ribosome collisions; translation},
   language = {eng},
   issn = {1097-2765},
   journal = {Molecular Cell},
   title = {Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes},
   url = {https://www.sciencedirect.com/science/article/pii/S1097276524008694?via%3Dihub},
   volume = {84},
   year = {2024}
}

TY  - JOUR
ID  - 65046
AU  - Kim, Kyusik Q. - Li, Jeffrey J. - Urs Nanjaraj, Ankanahalli N. - Pacheco, Miguel E. - Lasehinde, Victor - Denk, Timo - Těšina, Petr - Tomomatsu, Shota - Matsuo, Yoshitaka - McDonald, Elesa - Beckmann, Roland - Inada, Toshifumi - Green, Rachel - Zaher, Hani S.
PY  - 2024
TI  - Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes
JF  - Molecular Cell
VL  - 84
IS  - 23
SP  - 1-28
EP  - 1-28
PB  - CELL PRESS
SN  - 1097-2765
KW  - Gcn2
KW  - Gcn4
KW  - Mbf1
KW  - integrated stress response
KW  - ribosome
KW  - ribosome collisions
KW  - translation
UR  - https://www.sciencedirect.com/science/article/pii/S1097276524008694?via%3Dihub
N2  - In yeast, multiprotein bridging factor 1 (Mbf1) has been proposed to function in the integrated stress response (ISR) as a transcriptional coactivator by mediating a direct interaction between general transcription machinery and the process's key effector, Gcn4. However, mounting evidence has demonstrated that Mbf1 (and its human homolog EDF1) is recruited to collided ribosomes, a known activator of the ISR. In this study, we connect these otherwise seemingly disparate functions of Mbf1. Our biochemical and structural analyses reveal that Mbf1 functions as a core ISR factor by interacting with collided ribosomes to mediate Gcn2 activation. We further show that Mbf1 serves no role as a transcriptional coactivator of Gcn4. Instead, Mbf1 is required for optimal stress-induced eukaryotic initiation factor 2alpha (eIF2alpha) phosphorylation and downstream de-repression of GCN4 translation. Collectively, our data establish that Mbf1 functions in ISR signaling by acting as a direct sensor of stress-induced ribosome collisions.
ER  -

KIM, Kyusik Q.; Jeffrey J. LI; Ankanahalli N. URS NANJARAJ; Miguel E. PACHECO; Victor LASEHINDE; Timo DENK; Petr TĚŠINA; Shota TOMOMATSU; Yoshitaka MATSUO; Elesa MCDONALD; Roland BECKMANN; Toshifumi INADA; Rachel GREEN and Hani S. ZAHER. Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes. \textit{Molecular Cell}. CAMBRIDGE: CELL PRESS, 2024, vol.~84, No~23, p.~1-28. ISSN~1097-2765. Available from: https://dx.doi.org/10.1016/j.molcel.2024.10.029.