Prefoldin Plays a Role as a Clearance Factor in Preventing Proteasome Inhibitor-induced Protein Aggregation

Abe, Akira; Takahashi-Niki, Kazuko; Takekoshi, Yuka; Shimizu, Takashi; Kitaura, Hirotake; Maita, Hiroshi; Iguchi‐Ariga, Sanae M.M.; Ariga, Hiroyoshi

doi:10.1074/jbc.m113.476358

Cited by 39 publications

(42 citation statements)

References 25 publications

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“…Since the prefoldin complex contains two -type subunits (PFD3 and PFD5) and four -type subunits (PFD1, PFD2, PFD4 and PFD6), siRNAs targeting PFD5 (-type subunit) and PFD2 (-type subunit) were chosen for knockdown. As previously reported (Miyazawa et al, 2011;Tashiro et al, 2013;Abe et al, 2013), knockdown of either PFD2 or PFD5 reduced the expression levels of other prefoldin subunits (Fig. 3A) and knockdown of PFD2 and PFD5 disrupted the prefoldin complex detected by a glycerol density gradient centrifugation (data not shown).…”

Section: Stimulation Of -Synuclein Aggregation and Cell Death In Presupporting

confidence: 60%

Prefoldin prevents aggregation of α-synuclein

et al. 2014

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Protein aggregation is observed in various neurodegeneration diseases, including Parkinson's disease (PD). Alpha-synuclein, a causative gene product of familial PD, is a major component of large aggregates (inclusion bodies) in PD. Prefoldin, a molecular chaperone comprised of six subunits, PFD1~6, prevents misfolding of newly synthesized nascent polypeptides and also prevents aggregation of protein such as a pathogenic form of Huntingtin, a causative gene product of Huntington disease. In this study, we first found that aggregation of TagRFP-tagged wild-type -synuclein and its pathogenic mutants, but not that of GFP-tagged -synuclein,

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Section: Stimulation Of -Synuclein Aggregation and Cell Death In Presupporting

confidence: 60%

Prefoldin prevents aggregation of α-synuclein

et al. 2014

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“…Expression of Dnajb14 was reported to accelerate the degradation of misfolded membrane proteins such as the cystic fibrosis transmembrane conductance regulator Δ508 (CFTRΔ508) [64]. Prefoldins were previously reported to prevent ubiquitinated-protein aggregation under ER-stress [65-67]. Up-regulation of these two molecular chaperones can be correlated with the improved homeostasis of P23H opsin in NIH3T3 cells.…”

Section: Resultsmentioning

confidence: 99%

Transcriptome profiling of NIH3T3 cell lines expressing opsin and the P23H opsin mutant identifies candidate drugs for the treatment of retinitis pigmentosa

Chen

Brooks

Gieser

et al. 2017

Pharmacological Research

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Mammalian cells are commonly employed in screening assays to identify active compounds that could potentially affect the progression of different human diseases including retinitis pigmentosa (RP), a class of inherited diseases causing retinal degeneration with compromised vision. Using transcriptome analysis, we compared NIH3T3 cells expressing wildtype (WT) rod opsin with a retinal disease-causing single P23H mutation. Surprisingly, heterologous expression of WT opsin in NIH3T3 cells caused more than a 2-fold change in 783 out of 16,888 protein coding transcripts. The perturbed genes encoded extracellular matrix proteins, growth factors, cytoskeleton proteins, glycoproteins and metalloproteases involved in cell adhesion, morphology and migration. A different set of 347 transcripts was either up- or down-regulated when the P23H mutant opsin was expressed suggesting an altered molecular perturbation compared to WT opsin. Transcriptome perturbations elicited by drug candidates aimed at mitigating the effects of the mutant protein revealed that different drugs targeted distinct molecular pathways that resulted in a similar phenotype selected by a cell-based high-throughput screen. Thus, transcriptome profiling can provide essential information about the therapeutic potential of a candidate drug to restore normal gene expression in pathological conditions.

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“…However, a more in-depth review of the scientific literature reveals that eukaryotic prefoldin has also been connected to phenomena that are not directly linked to the cytoskeleton, such as protein aggregation. Prefoldin prevents protein aggregation in brain cells under conditions where protein degradation is compromised [24]. This role of prefoldin explains its protective effect against polyglutamine toxicity and the accumulation of aggregated pathogenic huntingtin [25].…”

Section: Introductionmentioning

confidence: 99%

Nuclear functions of prefoldin

Millán-Zambrano

Chávez

2014

Open Biol.

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Prefoldin is a cochaperone, present in all eukaryotes, that cooperates with the chaperonin CCT. It is known mainly for its functional relevance in the cytoplasmic folding of actin and tubulin monomers during cytoskeleton assembly. However, both canonical and prefoldin-like subunits of this heterohexameric complex have also been found in the nucleus, and are functionally connected with nuclear processes in yeast and metazoa. Plant prefoldin has also been detected in the nucleus and physically associated with a gene regulator. In this review, we summarize the information available on the involvement of prefoldin in nuclear phenomena, place special emphasis on gene transcription, and discuss the possibility of a global coordination between gene regulation and cytoplasmic dynamics mediated by prefoldin.

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Prefoldin Plays a Role as a Clearance Factor in Preventing Proteasome Inhibitor-induced Protein Aggregation

Cited by 39 publications

References 25 publications

Prefoldin prevents aggregation of α-synuclein

Prefoldin prevents aggregation of α-synuclein

Transcriptome profiling of NIH3T3 cell lines expressing opsin and the P23H opsin mutant identifies candidate drugs for the treatment of retinitis pigmentosa

Nuclear functions of prefoldin

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