Přehled o publikaci
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.Základní údaje
Originální název
Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes
Autoři
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 a Hani S. ZAHER
Vydání
Molecular Cell, CAMBRIDGE, CELL PRESS, 2024, 1097-2765
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Organizace
Středoevropský technologický institut – Masarykova univerzita – Repozitář
UT WoS
001376472600001
EID Scopus
2-s2.0-85210612902
Klíčová slova anglicky
Gcn2; Gcn4; Mbf1; integrated stress response; ribosome; ribosome collisions; translation
Návaznosti
LX22NPO5103, projekt VaV.
Změněno: 28. 1. 2025 00:50, RNDr. Daniel Jakubík
Anotace
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.