The GST-BHMT assay reveals a distinct mechanism underlying proteasome inhibition-induced macroautophagy in mammalian cells

Rui, Yanning; Xu, Zhen; Chen, Zhihua; Zhang, Sheng

doi:10.1080/15548627.2015.1034402

Cited by 8 publications

(6 citation statements)

References 61 publications

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“…Xia et al (25) have revealed that high expression of P4HB in liver cancer tissues was associated with poor survival. However, there is also evidence suggesting that the low expression of P4HB could lead to proteasome inhibition-induced autophagy (78), since the boundary between apoptosis and autophagy has always been controversial due to tumor heterogeneity (79). Based on the present results revealing that the patients with hypermethylation and low expression of P4HB had poor prognosis, it was hypothesized that hypermethylation of P4HB in prostate cancer would activate autophagy of prostate cancer cells and promote the tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Identification of aberrantly methylated‑differentially expressed genes and gene ontology in prostate cancer

Wang

Wang²,

Quan

2019

Mol Med Report

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Prostate cancer (Pca) is the most frequent urological malignancy in men worldwide. dna methylation has an essential role in the etiology and pathogenesis of Pca. The purpose of the present study was to identify the aberrantly methylated-differentially expressed genes and to determine their potential roles in Pca. The important node genes identified were screened by integrated analysis. Gene expression microarrays and gene methylation microarrays were downloaded and aberrantly methylated-differentially expressed genes were obtained. enrichment analysis and protein-protein interactions (PPi) were obtained, their interactive and visual networks were created, and the node genes in the PPi network were validated. a total of 105 hypomethylation-high expression genes and 561 hypermethylation-low expression genes along with their biological processes were identified. The top 10 node genes obtained from the PPI network were identified for each of the two gene groups. The methylation and gene expression status of node genes in TCGA database, GEPIA tool, and the HPa database were generally consistent with those of our results. In conclusion, the present study identified 20 aberrantly methylated-differentially expressed genes in Pca by combining bioinformatics analyses of gene expression and gene methylation microarrays, and concurrently, the survival of these genes was analyzed. notably, methylation is a reversible biological process, which makes it of great biological significance for the diagnosis and treatment of prostate cancer using bioinformatics technology to determine abnormal methylation gene markers. The present study provided novel therapeutic targets for the treatment of Pca.

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Section: Discussionmentioning

confidence: 99%

Identification of aberrantly methylated‑differentially expressed genes and gene ontology in prostate cancer

Wang

Wang²,

Quan

2019

Mol Med Report

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“…Similarly, treatment with MG132 or bortezomib in human colon cancer cells produced ER-stress and UPR dependent autophagy activation. Autophagy was abolished by IRE1α knockdown, or by treatment with the JNK inhibitor SP600125 (Ding et al, 2007), but was independent of XBP-1 signaling (Ding et al, 2007;Rui et al, 2015). Finally, proteasome inhibition with bortezomib in human prostate cancer cells, and immortalized mouse embryonic fibroblasts promoted autophagy activation and upregulated expression of ATG5 and ATG7, which depended on phosphorylation of eIF2α, a downstream element of the PERK arm of the UPR (Zhu et al, 2010).…”

Section: Pharmacological Approachesmentioning

confidence: 95%

Proteostasis Dysfunction in Aged Mammalian Cells. The Stressful Role of Inflammation

Ruano

2021

Front. Mol. Biosci.

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Aging is a biological and multifactorial process characterized by a progressive and irreversible deterioration of the physiological functions leading to a progressive increase in morbidity. In the next decades, the world population is expected to reach ten billion, and globally, elderly people over 80 are projected to triple in 2050. Consequently, it is also expected an increase in the incidence of age-related pathologies such as cancer, diabetes, or neurodegenerative disorders. Disturbance of cellular protein homeostasis (proteostasis) is a hallmark of normal aging that increases cell vulnerability and might be involved in the etiology of several age-related diseases. This review will focus on the molecular alterations occurring during normal aging in the most relevant protein quality control systems such as molecular chaperones, the UPS, and the ALS. Also, alterations in their functional cooperation will be analyzed. Finally, the role of inflammation, as a synergistic negative factor of the protein quality control systems during normal aging, will also be addressed. A better comprehension of the age-dependent modifications affecting the cellular proteostasis, as well as the knowledge of the mechanisms underlying these alterations, might be very helpful to identify relevant risk factors that could be responsible for or contribute to cell deterioration, a fundamental question still pending in biomedicine.

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“…However, Rui et al provided inconsistent data that under nutrient-rich conditions, inactivation of proteasome function induced an autophagy-dependent process and relied on the critical autophagy components ATG7 and ULK1, but is not involved the upstream autophagy regulators MTORC1 or AMPK. Further, the authors demonstrated that it otherwise depends on ER stress pathway (20).…”

Section: Introductionmentioning

confidence: 97%

Autophagy Induced by Proteasomal DUB Inhibitor NiPT Restricts NiPT-Mediated Cancer Cell Death

Chen

et al. 2020

Front. Oncol.

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Ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP) are two major systems for protein quality control (PQC) in eukaryotic cells. Interconnectivity between these two pathways has been suggested, but the molecular detail of how they impact each other remains elusive. Proteasomal deubiquitinase (DUB) is an important constituent in the UPS and has proved to be a novel anticancer target. We have previously found that a novel DUB inhibitor, nickel complex NiPT, induces apoptosis in both cultured tumor cell lines and cancer cells from acute myeloid leukemia human patients. In this study, we found that NiPT triggered autophagy both in vitro and in vivo. Mechanistically, NiPT targets two DUBs, USP14, and UCHL5, and increased the total cellular level of polyubiquitination. Deletion of the Ubiquitin Associated (UBA) domain of P62 that is required for polyubiquitin binding prevented NiPT-induced autophagy. NiPTinduced autophagy is through either concomitant activation of AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin (mTOR) signaling, or eliciting endoplasmic reticulum (ER)-stress by activating activating transcription factor 4 (ATF4) and C/EBP-homologous protein (CHOP). Moreover, NiPT could induce more lung cancer cells undergoing apoptosis if it synergistically uses autophagy inhibitors, suggesting that NiPT-induced autophagy protects cancer cell from death. Collectively, our findings demonstrate that autophagy inhibition enhances the anticancer effects of proteasomal DUB inhibitor and might be an effective treatment strategy for lung cancer.

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The GST-BHMT assay reveals a distinct mechanism underlying proteasome inhibition-induced macroautophagy in mammalian cells

Cited by 8 publications

References 61 publications

Identification of aberrantly methylated‑differentially expressed genes and gene ontology in prostate cancer

Identification of aberrantly methylated‑differentially expressed genes and gene ontology in prostate cancer

Proteostasis Dysfunction in Aged Mammalian Cells. The Stressful Role of Inflammation

Autophagy Induced by Proteasomal DUB Inhibitor NiPT Restricts NiPT-Mediated Cancer Cell Death

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