... proteinopathies; however, the precise defects underlying these disorders are unclear. Here, we systematically investigate the role of p97 and its adaptors in the process of formation of aggresomes, membrane-less structures containing ubiquitylated proteins that arise upon proteasome inhibition. We demonstrate...

... puncta Phosphorylation Phase transition Aggresome National Institutes of Health 10.13039/100000002 NS24821 DA025896 5R21MH086853 Türkiye Bilimsel ve Teknolojik Araştirma Kurumu Fig. 4. Analysis of AGS3 phosphorylation status and subcellular positioning of AGS3...

...Chenliang Zhang; Ju Gao; Mengen Li; Yongkang Deng; Changan Jiang ABSTRACT Aggresome formation is a major strategy to enable cells to cope with proteasomal stress. Misfolded proteins are assembled into micro-aggregates and transported to the microtubule organizing center (MTOC) to form perinuclear...

... as ‘aggresomes’. The roles of aggresomes as cellular quality control centers, and the cellular origin of the deposits contained within these structures, remain to be characterized. Here, we utilized the observation that the prion protein (PrP, also known as PRNP) accumulates in aggresomes following...

... for processing and degradation at perinuclear aggresomes. Disruption of this process leads to dysfunctional endosome accumulation and increased protein aggregation in the cell cytoplasm, both pathological features of neurodegenerative diseases. However, the exact mechanism of dynein functionality...

...Zhe Xu; Kourtney Graham; Molly Foote; Fengshan Liang; Raed Rizkallah; Myra Hurt; Yanchang Wang; Yuying Wu; Yi Zhou Summary The aggresome is a key cytoplasmic organelle for sequestration and clearance of toxic protein aggregates. Although loading misfolded proteins cargos to dynein motors has been...

... with high basal PHD3 expression, such as placenta, the aggregates were clearly less abundant and smaller ( Fig. 1A ). Fig. 1. Colocalization of p62 with PHD3. ( A ) PHD3 forms juxtanuclear aggresome-like structures (arrows) in carcinomas. Immunohistochemical analysis of PHD3 expression in paraffin...

...Anatoli B. Meriin; Nava Zaarur; Michael Y. Sherman Aggresome formation is initiated upon proteasome failure, and facilitates autophagic clearance of protein aggregates to protect cells from proteotoxicity. Here we demonstrate that proteasome inhibition generates a signaling event to trigger...

... and prone to aggregation, and they are selectively degraded by both the proteasome and aggresome–autophagy pathways. Our findings suggest that SIMPLE mutations cause CMT1C peripheral neuropathy by a combination of loss-of-function and toxic gain-of-function mechanisms, and highlight the importance of both...

...Yoshihisa Watanabe; Masaki Tanaka Proteolytic systems and the aggresome pathway contribute to preventing accumulation of cytotoxic aggregation-prone proteins. Although polyubiquitylation is usually required for degradation or aggresome formation, several substrates are processed independently...

... have been found to accumulate in juxtanuclear deposition sites termed ‘aggresomes’. Recently, it was shown that cells can contain at least two types of deposition sites for misfolded proteins: a dynamic quality-control compartment, which was termed ‘JUNQ’, and a site for terminally aggregated proteins...

...Masahiko Watabe; Toshio Nakaki Misfolded protein aggregates elicit a stress response, and their clearance is crucial for cell survival. These aggregates are transported by cytoplasmic deacetylase HDAC6 and dynein motors to the aggresome via the microtubule network, and are removed by autophagic...

...Birte Kalveram; Gunter Schmidtke; Marcus Groettrup During misfolded-protein stress, the cytoplasmic protein histone deacetylase 6 (HDAC6) functions as a linker between the dynein motor and polyubiquitin to mediate the transport of polyubiquitylated cargo to the aggresome. Here, we identify a new...

... nucleator Arp2/3. This aggregate was tightly associated with the Golgi complex and mitochondria, and was surrounded by vimentin intermediate filaments, microtubules and MAP4. Therefore, the Jpk-induced single, large F-actin aggregate fits the established criteria for being considered an aggresome. Lysosomes...

.../p25 inhibited cell division and promoted cell death. At high expression levels or in the presence of proteosome inhibitor, green fusion protein accumulated around centrosomes forming an aggresome-like structure protruding into the nucleus or a filamentous cage of microtubules surrounding the nucleus...

... Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan 22 4 2004 © The Company of Biologists Limited 2004 2004 Aggresome Atg5 Autophagy BEACH domain FYVE domain PI-3-kinase Phosphoinositides, phosphorylated derivatives of the membrane lipid...

... proteins accumulated as dispersed aggregates rather than as single aggresomes, even in the presence of proteasome inhibitors, which normally promote aggresome formation. RNAi of VCP caused extensive vacuolization of the cytoplasm, and proteasome inhibitors exaggerated this feature. RNAi of VCP had little...

..., M. L., Tu, P.-H., Iwatsubo, T. and Trojanowski, J. Q. ( 1999 ). Pathobiology of the Lewy Body. In Parkinson's Disease. Philadelphia, PA: Lippincott Williams & Wilkins. Garcia-Mata, R., Bebok, Z., Sorscher, E. J. and Sztul, E. S. ( 1999 ). Characterization and dynamics of aggresome...

... in juxtanuclear aggregates meeting the main criterions of aggresomes and leading to profound alterations of the mitochondrial network. The viability of cells transfected by intracellular forms of clusterin was improved by overexpression of Bcl-2,and caspase inhibition was capable of rescuing cells expressing...

..., a facilitator of trafficking of other misfolded proteins, attenuated the aggregation of EGFP/hSP-C ΔExon4 . We conclude that c.460+1A>G mutation of human SP-C results in disruption of disulfide-mediated folding encoded by Exon 4 leading to diversion of unprocessed proSP-C to aggresomes. The heterotypic...