한빛사 논문
Jeeyoon Chang1,2, Hyun Jung Hwang1,2, Byungju Kim3, Yeon-Gil Choi2, Joori Park1,2, Yeonkyoung Park1,2, Ban Seok Lee1,2, Heedo Park4, Min Ji Yoon2, Jae-Sung Woo2, Chungho Kim2, Man-Seong Park4, Jong-Bong Lee3, Yoon Ki Kim1,2,*
1Creative Research Initiatives Center for Molecular Biology of Translation, Korea University, Seoul 02841, Republic of Korea.
2Division of Life Sciences, Korea University, Seoul 02841, Republic of Korea.
3School of Interdisciplinary Bioscience and Bioengineering, POSTECH, Pohang 37673, Republic of Korea.
4Department of Microbiology, Institute for Viral Diseases, College of Medicine, Korea University, Seoul 02841, Republic of Korea.
*Corresponding author
Abstract
Selective recognition and elimination of misfolded polypeptides are crucial for protein homeostasis. When the ubiquitin-proteasome system is impaired, misfolded polypeptides tend to form small cytosolic aggregates and are transported to the aggresome and eventually eliminated by the autophagy pathway. Despite the importance of this process, the regulation of aggresome formation remains poorly understood. Here, we identify TRIM28/TIF1β/KAP1 (tripartite motif containing 28) as a negative regulator of aggresome formation. Direct interaction between TRIM28 and CTIF (cap binding complex dependent translation initiation factor) leads to inefficient aggresomal targeting of misfolded polypeptides. We also find that either treatment of cells with poly I:C or infection of the cells by influenza A viruses triggers the phosphorylation of TRIM28 at S473 in a way that depends on double-stranded RNA-activated protein kinase. The phosphorylation promotes association of TRIM28 with CTIF, inhibits aggresome formation, and consequently suppresses viral proliferation. Collectively, our data provide compelling evidence that TRIM28 is a negative regulator of aggresome formation.
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