Order through destruction: how ER‐associated protein degradation contributes to organelle homeostasis

The EMBO Journal, Год журнала: 2022, Номер 41(6)

Опубликована: Фев. 16, 2022

The endoplasmic reticulum (ER) is a large, dynamic, and multifunctional organelle. ER protein homeostasis essential for the coordination of its diverse functions depends on ER-associated degradation (ERAD). latter process selects target proteins in lumen membrane ER, promotes their ubiquitination, facilitates delivery into cytosol by proteasome. Originally characterized role misfolded rate-limiting enzymes sterol biosynthesis, many branches ERAD now appear to control levels wider range substrates influence more broadly organization as well interactions with adjacent organelles. Here, we discuss recent mechanistic advances our understanding consequences regulation functions.

Язык: Английский

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Protein Misfolding and Aggregation in Proteinopathies: Causes, Mechanism and Cellular Response

Diseases, Год журнала: 2023, Номер 11(1), С. 30 - 30

Опубликована: Фев. 9, 2023

Proteins are central to life functions. Alterations in the structure of proteins reflected their function. Misfolded and aggregates present a significant risk cell. Cells have diverse but integrated network protection mechanisms. Streams misfolded that cells continuously exposed must be continually monitored by an elaborated molecular chaperones protein degradation factors control contain misfolding problems. Aggregation inhibition properties small molecules such as polyphenols important they possess other beneficial antioxidative, anti-inflammatory, pro-autophagic help neuroprotection. A candidate with desired features is for any possible treatment development aggregation diseases. There need study phenomenon so we can treat some worst kinds human ailments related aggregation.

Язык: Английский

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Upstream and downstream regulators of Klotho expression in chronic kidney disease

Metabolism, Год журнала: 2023, Номер 142, С. 155530 - 155530

Опубликована: Март 1, 2023

Klotho is a critical protein that protects the kidney. severely downregulated in chronic kidney disease (CKD), and its deficiency implicated pathogenesis progression of CKD. Conversely, an increase levels results improved function delays CKD progression, supporting notion modulating could represent possible therapeutic strategy for treatment. Nevertheless, regulatory mechanisms responsible loss remain elusive. Previous studies have demonstrated oxidative stress, inflammation, epigenetic modifications can modulate levels. These result decrease mRNA transcript reduced translation, thus be grouped together as upstream mechanisms. However, strategies aim to rescue by targeting these do not always increased Klotho, indicating involvement other Emerging evidence has shown endoplasmic reticulum (ER) unfolded response, ER-associated degradation also affect modification, translocation, are proposed downstream Here, we discuss current understanding examine potential upregulate expression

Язык: Английский

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Role of cell membrane homeostasis in the pathogenicity of pathogenic filamentous fungi

Virulence, Год журнала: 2023, Номер 15(1)

Опубликована: Дек. 29, 2023

The cell membrane forms a fundamental part of all living cells and participates in variety physiological processes, such as material exchange, stress response, recognition, signal transduction, cellular immunity, apoptosis, pathogenicity. Here, we review the mechanisms functions structure (lipid components biosynthesis unsaturated fatty acids), proteins (transmembrane contributing to curvature), transcriptional regulation, wall that influence virulence pathogenicity filamentous fungi.

Язык: Английский

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Pathways of MHC I cross-presentation of exogenous antigens

Seminars in Immunology, Год журнала: 2023, Номер 66, С. 101729 - 101729

Опубликована: Фев. 16, 2023

Язык: Английский

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PD-L1 translocation to the plasma membrane enables tumor immune evasion through MIB2 ubiquitination

Journal of Clinical Investigation, Год журнала: 2023, Номер 133(3)

Опубликована: Янв. 31, 2023

Programmed death-ligand 1 (PD-L1), a critical immune checkpoint ligand, is transmembrane protein synthesized in the endoplasmic reticulum of tumor cells and transported to plasma membrane interact with programmed death (PD-1) expressed on T cell surface. This interaction delivers coinhibitory signals cells, thereby suppressing their function allowing evasion antitumor immunity. Most companion or complementary diagnostic devices for assessing PD-L1 expression levels used clinic clinical trials require membranous staining. However, mechanism driving translocation after de novo synthesis poorly understood. Herein, we showed that mind bomb homolog 2 (MIB2) required transportation from trans-Golgi network (TGN) cancer cells. MIB2 deficiency led fewer proteins surface promoted immunity mice. Mechanistically, catalyzed nonproteolytic K63-linked ubiquitination PD-L1, facilitating trafficking through Ras-associated binding 8-mediated (RAB8-mediated) exocytosis TGN membrane, where it bound PD-1 extrinsically prevent killing by Our findings demonstrate its evasion.

Язык: Английский

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Hydrophobic tag-based protein degradation: Development, opportunity and challenge

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 260, С. 115741 - 115741

Опубликована: Авг. 19, 2023

Язык: Английский

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E3 ligase autoinhibition by C-degron mimicry maintains C-degron substrate fidelity

Molecular Cell, Год журнала: 2023, Номер 83(5), С. 770 - 786.e9

Опубликована: Фев. 16, 2023

Язык: Английский

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Efficient Plant Triterpenoids Synthesis in Saccharomyces cerevisiae: from Mechanisms to Engineering Strategies

ACS Synthetic Biology, Год журнала: 2024, Номер 13(4), С. 1059 - 1076

Опубликована: Март 28, 2024

Triterpenoids possess a range of biological activities and are extensively utilized in the pharmaceutical, food, cosmetic, chemical industries. Traditionally, they acquired through synthesis plant extraction. However, these methods have drawbacks, including high energy consumption, environmental pollution, being time-consuming. Recently, de novo triterpenoids microbial cell factories has been achieved. This represents promising environmentally friendly alternative to traditional supply methods. Saccharomyces cerevisiae, known for its robustness, safety, ample precursor supply, stands out as an ideal candidate triterpenoid biosynthesis. challenges persist industrial production economic feasibility Consequently, metabolic engineering approaches applied improve yield, leading substantial progress. review explores biosynthesis mechanisms S. cerevisiae strategies efficient production. Finally, also discusses current proposes potential solutions, offering insights future engineering.

Язык: Английский

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Mechanical effect of protein glycosylation on BiP-mediated post-translational translocation and folding in the endoplasmic reticulum

Biophysical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

Язык: Английский

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