Mutation in the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct5) gene causes autosomal recessive mutilating sensory neuropathy with spastic paraplegia

Bouhouche, Ahmed

doi:10.1136/jmg.2005.039230

Cited by 115 publications

(88 citation statements)

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“…Arsenic inhibition of TRiC might thus indirectly downregulate p53 activity and cause cancers, a model consistent with the observation that arsenic inhibits p53 activation in response to DNA damage (Tang et al 2006). In addition, mutating TRiC subunit genes CCT5 and CCT4 are directly implicated in sensory neuropathy in both human patients and in a rat model (Lee et al 2003;Bouhouche et al 2006). …”

Section: Discussionmentioning

confidence: 65%

“…This mechanism of action is apparently conserved because the activities of both a mammalian TRiC complex and an archaeal TRiClike chaperonin are significantly inhibited by arsenic in vitro. Given that mammalian TRiC and some of its substrates are implicated in tumor suppression, angiogenesis, and neuropathy (Lee et al 2003;Spiess et al 2004;Bouhouche et al 2006), TRiC is likely an important protein mediator of As(III)'s effects on human health.…”

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confidence: 99%

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Trivalent Arsenic Inhibits the Functions of Chaperonin Complex

et al. 2010

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The exact molecular mechanisms by which the environmental pollutant arsenic works in biological systems are not completely understood. Using an unbiased chemogenomics approach in Saccharomyces cerevisiae, we found that mutants of the chaperonin complex TRiC and the functionally related prefoldin complex are all hypersensitive to arsenic compared to a wild-type strain. In contrast, mutants with impaired ribosome functions were highly arsenic resistant. These observations led us to hypothesize that arsenic might inhibit TRiC function, required for folding of actin, tubulin, and other proteins postsynthesis. Consistent with this hypothesis, we found that arsenic treatment distorted morphology of both actin and microtubule filaments. Moreover, arsenic impaired substrate folding by both bovine and archaeal TRiC complexes in vitro. These results together indicate that TRiC is a conserved target of arsenic inhibition in various biological systems.

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Section: Discussionmentioning

confidence: 65%

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confidence: 99%

Trivalent Arsenic Inhibits the Functions of Chaperonin Complex

et al. 2010

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“…13,14,18,20 Likewise, CCT5, KIF1A, and DYNC1H1 are other genes encoding motor proteins that have an important role in axonal transport and their mutations have been identified in patients with complex syndromes involving both the peripheral nervous system and CNS. [21][22][23][24] Thus axonal transport represents a potential common pathway in the pathogenesis of both axonal neuropathy and spastic paraplegia. 20 …”

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confidence: 99%

Extended phenotypic spectrum of KIF5A mutations

et al. 2014

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Objective: To establish the phenotypic spectrum of KIF5A mutations and to investigate whether KIF5A mutations cause axonal neuropathy associated with hereditary spastic paraplegia (HSP) or typical Charcot-Marie-Tooth disease type 2 (CMT2).Methods: KIF5A sequencing of the motor-domain coding exons was performed in 186 patients with the clinical diagnosis of HSP and in 215 patients with typical CMT2. Another 66 patients with HSP or CMT2 with pyramidal signs were sequenced for all exons of KIF5A by targeted resequencing. One additional patient was genetically diagnosed by whole-exome sequencing.Results: Five KIF5A mutations were identified in 6 unrelated patients: R204W and D232N were novel mutations; R204Q, R280C, and R280H have been previously reported. Three patients had CMT2 as the predominant and presenting phenotype; 2 of them also had pyramidal signs. The other 3 patients presented with HSP but also had significant axonal neuropathy or other additional features.Conclusion: This is currently the largest study investigating KIF5A mutations. By combining nextgeneration sequencing and conventional sequencing, we confirm that KIF5A mutations can cause variable phenotypes ranging from HSP to CMT2. The identification of mutations in CMT2 broadens the phenotypic spectrum and underlines the importance of KIF5A mutations, which involve degeneration of both the central and peripheral nervous systems and should be tested in HSP and CMT2. Neurology ® 2014;83:612-619 GLOSSARY CMT2 5 Charcot-Marie-Tooth disease type 2; HSP 5 hereditary spastic paraplegia; KHC 5 kinesis heavy chain; SPG10 5 spastic paraplegia type 10; WES 5 whole-exome sequencing.

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“…TCP-1 is one of the subunits of chaperonin-containing TCP-1 (CCT), a hetero-oligomeric ring complex composed of 8 subunits (␣, ␤, ␥, ␦, , , , and ) (Llorca et al 2001;Bouhouche et al 2006). CCT is necessary for the folding of actin and tubulin in the cytosol.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis of rat hepatic stellate cells induced by diallyl trisulfide and proteomics profiling in vitro

Zhang

Zhou

et al. 2017

Can. J. Physiol. Pharmacol.

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Diallyl trisulfide (DATS), a major garlic derivative, inhibits cell proliferation and triggers apoptosis in a variety of cancer cell lines. However, the effects of DATS on hepatic stellate cells (HSCs) remain unknown. The aim of this study was to analyze the effects of DATS on cell proliferation and apoptosis, as well as the protein expression profile in rat HSCs. Rat HSCs were treated with or without 12 and 24 g/mL DATS for various time intervals. Cell proliferation and apoptosis were determined using tetrazolium dye (MTT) colorimetric assay, bromodeoxyuridine (5-bromo-2=-deoxyuridine; BrdU) assay, Hoechst 33342 staining, electroscopy, and flow cytometry. Protein expression patterns in HSCs were systematically studied using 2-dimensional electrophoresis and mass spectrometry. DATS inhibited cell proliferation and induced apoptosis of HSCs in a time-dependent manner. We observed clear morphological changes in apoptotic HSCs and dramatically increased annexin V-positive -propidium iodide negative apoptosis compared with the untreated control group. Twenty-one significant differentially expressed proteins, including 9 downregulated proteins and 12 upregulated proteins, were identified after DATS administration, and most of them were involved in apoptosis. Our results suggest that DATS is an inducer of apoptosis in HSCs, and several key proteins may be involved in the molecular mechanism of apoptosis induced by DATS.Key words: diallyl trisulfide, apoptosis, hepatic stellate cells, differentially expressed proteins.Résumé : Le trisulfure de diallyle (TSDA), un dérivé important de l'ail, inhibe la prolifération cellulaire et déclenche l'apoptose dans une variété de lignées cellulaires cancéreuses. Cependant, les effets du TSDA sur les cellules de Kupffer (CK) restent inconnus. Cette étude visait à analyser les effets du TSDA sur la prolifération cellulaire et l'apoptose, de même que sur le profil d'expression des protéines dans les CK de rat. Les CK de rat ont été traitées ou non avec 12 et 24 g/mL de TSDA pendant différentes périodes de temps. La prolifération cellulaire et l'apoptose ont été déterminées à l'aide d'un dosage colorimétrique au tétrazolium (MTT), d'un dosage à la bromodéoxyuridine (5-bromo-2=-déoxyuridine, BrdU), par coloration au Hoechst 33342, par microscopie électronique et par cytométrie en flux. Les patrons d'expression protéique des CK ont été systématiquement étudiés par électrophorèse en deux dimensions et par spectroscopie de masse. Le TSDA inhibait la prolifération cellulaire et induisait l'apoptose des CK en fonction du temps. Les auteurs ont observé des changements morphologiques clairs des CK en apoptose et une augmentation importante des cellules en apoptose positives à l'annexine V et négatives à l'iodure de propidium comparativement au groupe contrôle non traité. Vingt et une protéines exprimées de façon différentielle, soit neuf protéines régulées à la baisse et 12 protéines régulées à la hausse, ont été identifiées à la suite de l'administration de TSDA, et la plupart d'ent...

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Mutation in the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct5) gene causes autosomal recessive mutilating sensory neuropathy with spastic paraplegia

Cited by 115 publications

References 20 publications

Trivalent Arsenic Inhibits the Functions of Chaperonin Complex

Trivalent Arsenic Inhibits the Functions of Chaperonin Complex

Extended phenotypic spectrum of KIF5A mutations

Apoptosis of rat hepatic stellate cells induced by diallyl trisulfide and proteomics profiling in vitro

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