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Publication Abstract from PubMed

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.

Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes.,Kim KQ, Li JJ, Nanjaraj Urs AN, Pacheco ME, Lasehinde V, Denk T, Tesina P, Tomomatsu S, Matsuo Y, McDonald E, Beckmann R, Inada T, Green R, Zaher HS Mol Cell. 2024 Nov 13:S1097-2765(24)00869-4. doi: 10.1016/j.molcel.2024.10.029. PMID:39566505^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.