title: C-terminally mutated tubby protein accumulates in aggresomes.
abstract: The tubby protein (Tub), a putative transcription factor, plays important roles in the maintenance and function of neuronal cells. A splicing defect-causing mutation in the 3'-end of the tubby gene, which is predicted to disrupt the carboxy-terminal region of the Tub protein, causes maturity-onset obesity, blindness, and deafness in mice. Although this pathological Tub mutation leads to a loss of function, the precise mechanism has not yet been investigated. Here, we found that the mutant Tub proteins were mostly localized to puncta found in the perinuclear region and that the C-terminus was important for its solubility. Immunocytochemical analysis revealed that puncta of mutant Tub co-localized with the aggresome. Moreover, whereas wild-type Tub was translocated to the nucleus by extracellular signaling, the mutant forms failed to undergo such translocation. Taken together, our results suggest that the malfunctions of the Tub mutant are caused by its misfolding and subsequent localization to aggresomes. [BMB Reports 2017; 50(1): 37-42].
authors.affiliation: Research Institute, National Cancer Center, Goyang 10408, Korea.
authors.forename: Sunshin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, Goyang 10408, Korea.
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Sung
authors.affiliation: Research Institute, National Cancer Center, Goyang 10408, Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Research Institute and Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Korea.
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Brain-Cognitive Science, Daegu-Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea.
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Oh
authors.affiliation: College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.
authors.forename: Kyong-Ah
authors.initials: KA
authors.lastname: Yoon
authors.affiliation: Research Institute, National Cancer Center, Goyang 10408, Korea.
authors.forename: Kyun
authors.initials: K
authors.lastname: Heo
authors.affiliation: School of Nano-Biotechnology and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Korea.
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000235:genetics; D066329:Protein Aggregates; D062106:Protein Degradation End Products / Q000378:metabolism; D017510:Protein Folding; D012326:RNA Splicing
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D066329:Protein Aggregates; D062106:Protein Degradation End Products; C098988:Tub protein, mouse