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

• Autoři: 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.
• Rok publikování: 2024
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: MOLECULAR CELL
• Fakulta / Pracoviště MU: Středoevropský technologický institut
• www: https://www.sciencedirect.com/science/article/pii/S1097276524008694?via%3Dihub
• Doi: https://doi.org/10.1016/j.molcel.2024.10.029
• Klíčová slova: Gcn2; Gcn4; Mbf1; integrated stress response; ribosome; ribosome collisions; translation

Přiložené soubory

• 1-s2.0-S1097276524008694-main.pdf
• 1-s2.0-S1097276524008694-main_B.pdf

• Popis: 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.

Související projekty

• Národní institut virologie a bakteriologie