Targeting mitochondrial transcription in fission yeast with ETB, an inhibitor of HSP60, the chaperone that binds to the mitochondrial transcription factor Mtf1

Sun, Wenxia; Wang, Li; Jiang, Hengyi; Chen, Dongrong; Murchie, Alastair I. H.

doi:10.1111/j.1365-2443.2011.01578.x

Cited by 8 publications

(5 citation statements)

References 36 publications

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“…One of the most studied Hsp60 inhibitors is epolactaene, a bacterial metabolite which inhibits the folding activity of human Hsp60, through covalent binding to Cys442 [ 79 ]. Epolactaene derivatives, such as the tertiary butyl ester ETB ( Figure 3 ), were also active [ 80 ] and SAR studies demonstrated that both the cyclic amide (lactam) and the α,β-unsaturated ketone are critical moieties for inhibiting the chaperone activity of Hsp60 [ 81 ]. An in-silico study suggested a putative mode of action for epolactaene, revealing the opening of a binding pocket in proximity of Cys442 after ATP occupies its binding site and that epolactaene covalently binds thiol moiety of Cys 442 through attack at C14 and epoxide ring-opening [ 82 ].…”

Section: Hsp60mentioning

confidence: 99%

Heat Shock Proteins in Alzheimer’s Disease: Role and Targeting

Campanella

Pace

Bavisotto

et al. 2018

IJMS

126

104

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Among diseases whose cure is still far from being discovered, Alzheimer’s disease (AD) has been recognized as a crucial medical and social problem. A major issue in AD research is represented by the complexity of involved biochemical pathways, including the nature of protein misfolding, which results in the production of toxic species. Considering the involvement of (mis)folding processes in AD aetiology, targeting molecular chaperones represents a promising therapeutic perspective. This review analyses the connection between AD and molecular chaperones, with particular attention toward the most important heat shock proteins (HSPs) as representative components of the human chaperome: Hsp60, Hsp70 and Hsp90. The role of these proteins in AD is highlighted from a biological point of view. Pharmacological targeting of such HSPs with inhibitors or regulators is also discussed.

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Section: Hsp60mentioning

confidence: 99%

Heat Shock Proteins in Alzheimer’s Disease: Role and Targeting

Campanella

Pace

Bavisotto

et al. 2018

IJMS

126

104

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“…Mtf1 has been characterized as a mitochondrial transcription factor and shown to regulate mitochondrial transcription. In fission yeast, MTF1 binds to Hsp60 in vivo and in vitro , and ETB inhibits the association of MTF1 and Hsp60, which represses mitochondrial transcription ( 32 ). The present study found that MTF1 had a significant positive correlation with mast cell activation.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of cuproptosis-related genes in immune infiltration in ischemic stroke

et al. 2023

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BackgroundImmune infiltration plays an important role in the course of ischemic stroke (IS) progression. Cuproptosis is a newly discovered form of programmed cell death. To date, no studies on the mechanisms by which cuproptosis-related genes regulate immune infiltration in IS have been reported.MethodsIS-related microarray datasets were retrieved from the Gene Expression Omnibus (GEO) database and standardized. Immune infiltration was extracted and quantified based on the processed gene expression matrix. The differences between the IS group and the normal group as well as the correlation between the infiltrating immune cells and their functions were analyzed. The cuproptosis-related DEGs most related to immunity were screened out, and the risk model was constructed. Finally, Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and drug target were performed using the Enrichr website database. miRNAs were predicted using FunRich software. Finally, cuproptosis-related differentially expressed genes (DEGs) in IS samples were typed, and Gene Set Variation Analysis (GSVA) was used to analyze the differences in biological functions among the different types.ResultsSeven Cuproptosis-related DEGs were obtained by merging the GSE16561 and GSE37587 datasets. Correlation analysis of the immune cells showed that NLRP3, NFE2L2, ATP7A, LIPT1, GLS, and MTF1 were significantly correlated with immune cells. Subsequently, these six genes were included in the risk study, and the risk prediction model was constructed to calculate the total score to analyze the risk probability of the IS group. KEGG analysis showed that the genes were mainly enriched in the following two pathways: D-glutamine and D-glutamate metabolism; and lipids and atherosclerosis. Drug target prediction found that DMBA CTD 00007046 and Lithocholate TTD 00009000 were predicted to have potential therapeutic effects of candidate molecules. GSVA showed that the TGF-β signaling pathway and autophagy regulation pathways were upregulated in the subgroup with high expression of cuproptosis-related DEGs.ConclusionsNLRP3, NFE2L2, ATP7A, LIPT1, GLS and MTF1 may serve as predictors of cuproptosis and play an important role in the pathogenesis of immune infiltration in IS.

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“…Recently, other derivatives of epolactaene (9), such as the epolactaene tertiary butyl ester (ETB) (10), were shown to target mitochondrial transcription [135]. A structure-activity relationship analysis performed on epolactaene derivatives demonstrated that both the cyclic amide (lactam) and the '-" unsaturated ketone are critical moieties for inhibiting the chaperone activity of HSP60 [129].…”

Section: Hsp60 Inhibitors and Their Potential Applications In Alzheimmentioning

confidence: 99%