PERK-dependent compartmentalization of ERAD and unfolded protein response machineries during ER stress

Kondratyev, Maria; Avezov, Edward; Shenkman, Marina; Groisman, Bella; Lederkremer, Gerardo Z.

doi:10.1016/j.yexcr.2007.07.006

Cited by 68 publications

(92 citation statements)

References 56 publications

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“…4, C-F). We had seen previously that these ERAD machinery components are recruited to the ERQC upon proteasomal inhibition or glycoprotein substrate overexpression (13,28). Although H2a⌬gly does not appear to bind to or require SCF Fbs2 for its degradation (Fig.…”

Section: Components Of the Glycoprotein Erad Pathway Target A Nonglycmentioning

confidence: 79%

“…26. H2a G78R uncleavable mutant fused through its C terminus to monomeric red fluorescent protein (H2a-RFP) was described previously (24,28). NS-1 LC and HA-␥ V-C H 1 constructs were described previously (Refs.…”

Section: Materials-rainbowmentioning

confidence: 99%

“…We next determined whether H2a⌬gly accumulates like WT H2a and other glycoprotein substrates in the juxtanuclear ERQC (8,12,28). Indeed, proteasomal inhibition caused accumulation of H2a⌬gly from an initial dispersed ER pattern to the ERQC, where it colocalized with the glycoprotein ERAD substrate H2a linked to a monomeric red fluorescent protein (H2a-RFP) (Fig.…”

Section: Components Of the Glycoprotein Erad Pathway Target A Nonglycmentioning

confidence: 99%

“…3), both proteins are still recruited to the ERQC, SCF Fbs2 apparently from the cytosolic side and H2a⌬gly on the membrane. This suggests that the ERQC may be a staging ground for ERAD of glycoproteins (13,28) as well as nonglycoproteins and that SCF Fbs2 is recruited either independent of the glycan nature of the substrate or that sufficient amounts of endogeneous glycoproteins exist to recruit it. H2a⌬gly remained separate from a Golgi marker, ␤1,3-galactosyltransferase linked to YFP (GalT-YFP) and also from most of the abundant ER chaperone BiP, which is not concentrated in the ERQC (Fig.…”

Section: Components Of the Glycoprotein Erad Pathway Target A Nonglycmentioning

confidence: 99%

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A Shared Endoplasmic Reticulum-associated Degradation Pathway Involving the EDEM1 Protein for Glycosylated and Nonglycosylated Proteins

Shenkman

Groisman

Ron

et al. 2013

Journal of Biological Chemistry

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Background: N-Glycan processing and interactions with lectins regulate the quality control and endoplasmic reticulumassociated degradation (ERAD) of glycoproteins. Results: Most of the same machinery targets nonglycosylated misfolded proteins. Conclusion: They share some membrane and luminal ERAD machinery but not all cytosolic components. Significance: ER glycan-interacting proteins must possess a dual specificity for glycan structure and for exposed misfolded polypeptide domains.

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Section: Components Of the Glycoprotein Erad Pathway Target A Nonglycmentioning

confidence: 79%

Section: Materials-rainbowmentioning

confidence: 99%

Section: Components Of the Glycoprotein Erad Pathway Target A Nonglycmentioning

confidence: 99%

Section: Components Of the Glycoprotein Erad Pathway Target A Nonglycmentioning

confidence: 99%

See 2 more Smart Citations

A Shared Endoplasmic Reticulum-associated Degradation Pathway Involving the EDEM1 Protein for Glycosylated and Nonglycosylated Proteins

Shenkman

Groisman

Ron

et al. 2013

Journal of Biological Chemistry

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“…In mammals, misfolded or slow folding secretory proteins are segregated into a domain referred to as the ER-derived quality control compartment (ERQC) [53][54][55][56].…”

Section: Eradmentioning

confidence: 99%

Genesis of ER stress in Huntington’s Disease

Shenkman

Eiger

Lederkremer

2015

Endoplasmic Reticulum Stress in Diseases

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Recent research has identified ER stress as a major mechanism implicated in cytotoxicity in many neurodegenerative diseases, among them Huntington’s disease. This genetic disorder is of late-onset, progressive and fatal, affecting cognition and movement. There is presently no cure nor any effective therapy for the disease. This review focuses on recent findings that shed light on the mechanisms of the advent and development of ER stress in Huntington’s disease and on its implications, highlighting possible therapeutic avenues that are being or could be explored.

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Combination of PolygonatumRhizoma and Scutellaria baicalensis triggers apoptosis through downregulation of PON₃‐induced mitochondrial damage and endoplasmic reticulum stress in A549 cells

Liu,

Yue,

et al. 2024

Environmental Toxicology

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ObjectiveScutellaria baicalensis (SB) and Polygonatum Rhizoma (PR), two traditional Chinese medicines, are both known to suppress cancer. However, the mechanism and effect of combined treatment of them for lung cancer are rarely known. Investigating the combined effect of SB and PR (hereafter referred to as SP) in potential mechanism of lung cancer is required. This study was to evaluate the inhibitory effects of SP on A549 cell growth and to explore the underlying molecular mechanisms.MethodsAccording to the theory of Chinese medicine and network pharmacology, in the in vivo experiment, a mouse model of carcinoma in situ was constructed, and lung carcinoma in situ tissues were collected for proteomics analysis, hematoxylin‐eosin staining, and CK19 immunohistochemistry. In the in vitro experiment, lung cancer A549 cells at logarithmic growth stage were taken, and the inhibitory effect of SP on the proliferation of A549 cells was detected by CCK8 method. The expression of PON3 was detected by quantitative polymerase chain reaction and western blot. In addition, the effect of SP on the induction of apoptosis in A549 cells and the changes of membrane potential and reactive oxygen species (ROS) content were detected by flow cytometry. The changes of PON3 content in endoplasmic reticulum (ER) are observed by laser confocal microscopy, whereas the effects of SP on the expression of apoptosis‐related proteins and ER stress‐related proteins in A549 cells were examined by western blot.ResultBy searching the Traditional Chinese Medicines of Systems Pharmacology (TCMSP) (https://www.tcmspe.com/index.php) database and SymMap database, the respective target genes of PR and SB were mapped into protein network interactions, and using Venn diagrams to show 38 genes in common between PR and SB and lung cancer, SP was found to play a role in the treatment of lung cancer. In vivo experiments showed that in a lung carcinoma in situ model, lung tumor tissue was significantly lower in the SP group compared with the control group, and PON3 was shown to be downregulated by lung tissue proteomics analysis. The combination of SP was able to inhibit the proliferation of A549 cells in a concentration‐dependent manner (p < .0001). The expression levels of apoptosis‐related proteins and ER stress proteins were significantly increased and the expression levels of PON3 and anti‐apoptosis‐related proteins were decreased in A549 cells. At the same time, knockdown of PON3 could inhibit tumor cell proliferation (p < .0001). The combination of different concentrations of SP significantly induced apoptosis in A549 cells (p < .05; p < .0001), increased ROS content (p < .01), and damaged mitochondrial membrane potential of A549 cells (p < .05; p < .0001), and significantly increased the expression levels of apoptosis‐related proteins and ER stress proteins in lung cancer A549 cells.ConclusionSP inhibits proliferation of lung cancer A549 cells by downregulating PON3‐induced apoptosis in the mitochondrial and ER pathways.

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PERK-dependent compartmentalization of ERAD and unfolded protein response machineries during ER stress

Cited by 68 publications

References 56 publications

A Shared Endoplasmic Reticulum-associated Degradation Pathway Involving the EDEM1 Protein for Glycosylated and Nonglycosylated Proteins

A Shared Endoplasmic Reticulum-associated Degradation Pathway Involving the EDEM1 Protein for Glycosylated and Nonglycosylated Proteins

Genesis of ER stress in Huntington’s Disease

Combination of PolygonatumRhizoma and Scutellaria baicalensis triggers apoptosis through downregulation of PON₃‐induced mitochondrial damage and endoplasmic reticulum stress in A549 cells

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PERK-dependent compartmentalization of ERAD and unfolded protein response machineries during ER stress

Cited by 68 publications

References 56 publications

A Shared Endoplasmic Reticulum-associated Degradation Pathway Involving the EDEM1 Protein for Glycosylated and Nonglycosylated Proteins

A Shared Endoplasmic Reticulum-associated Degradation Pathway Involving the EDEM1 Protein for Glycosylated and Nonglycosylated Proteins

Genesis of ER stress in Huntington’s Disease

Combination of PolygonatumRhizoma and Scutellaria baicalensis triggers apoptosis through downregulation of PON3‐induced mitochondrial damage and endoplasmic reticulum stress in A549 cells

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Combination of PolygonatumRhizoma and Scutellaria baicalensis triggers apoptosis through downregulation of PON₃‐induced mitochondrial damage and endoplasmic reticulum stress in A549 cells