한빛사 논문
Yeonkyoung Park1,2,5, Joori Park1,2,5, Hyun Jung Hwang1,2,5, Byungju Kim3,5, Kwon Jeong1,2, Jeeyoon Chang1,2, Jong-Bong Lee3,4,* & Yoon Ki Kim1,2,*
1Creative Research Initiatives Center for Molecular Biology of Translation, Korea University, Seoul 02841, Republic of Korea.
2School of Life Sciences, Korea University, Seoul 02841, Republic of Korea.
3Department of Physics, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
4School of Interdisciplinary Bioscience and Bioengineering, POSTECH, Pohang 37673, Republic of Korea.
5These authors contributed equally: Yeonkyoung Park, Joori Park, Hyun Jung Hwang, Byungju Kim.
*Corresponding author
Abstract
Nonsense-mediated mRNA decay (NMD) typifies an mRNA surveillance pathway. Because NMD necessitates a translation event to recognize a premature termination codon on mRNAs, truncated misfolded polypeptides (NMD-polypeptides) could potentially be generated from NMD substrates as byproducts. Here, we show that when the ubiquitin–proteasome system is overwhelmed, various misfolded polypeptides including NMD-polypeptides accumulate in the aggresome: a perinuclear nonmembranous compartment eventually cleared by autophagy. Hyperphosphorylation of the key NMD factor UPF1 is required for selective targeting of the misfolded polypeptide aggregates toward the aggresome via the CTIF–eEF1A1–DCTN1 complex: the aggresome-targeting cellular machinery. Visualization at a single-particle level reveals that UPF1 increases the frequency and fidelity of movement of CTIF aggregates toward the aggresome. Furthermore, the apoptosis induced by proteotoxic stresses is suppressed by UPF1 hyperphosphorylation. Altogether, our data provide evidence that UPF1 functions in the regulation of a protein surveillance as well as an mRNA quality control.
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