Endoplasmic reticulum stress in diseases

MedComm, Год журнала: 2024, Номер 5(9)

Опубликована: Авг. 26, 2024

The endoplasmic reticulum (ER) is a key organelle in eukaryotic cells, responsible for wide range of vital functions, including the modification, folding, and trafficking proteins, as well biosynthesis lipids maintenance intracellular calcium homeostasis. A variety factors can disrupt function ER, leading to aggregation unfolded misfolded proteins within its confines induction ER stress. conserved cascade signaling events known protein response (UPR) has evolved relieve burden restore However, these processes culminate cell death while stress sustained over an extended period at elevated levels. This review summarizes potential role UPR determining fate various diseases, cardiovascular neurodegenerative metabolic autoimmune fibrotic viral infections, cancer. It also puts forward that manipulation this intricate pathway may represent novel target drug discovery innovative therapeutic strategies context human diseases.

Язык: Английский

---

ACE2 in chronic disease and COVID-19: gene regulation and post-translational modification

Journal of Biomedical Science, Год журнала: 2023, Номер 30(1)

Опубликована: Авг. 22, 2023

Abstract Angiotensin-converting enzyme 2 (ACE2), a counter regulator of the renin-angiotensin system, provides protection against several chronic diseases. Besides diseases, ACE2 is host receptor for SARS-CoV or SARS-CoV-2 virus, mediating first step virus infection. levels are regulated by transcriptional, post-transcriptional, and post-translational regulation modification. transcription enhanced factors including Ikaros, HNFs, GATA6, STAT3 SIRT1, whereas reduced factor Brg1-FoxM1 complex ERRα. also histone modification miRNA-induced destabilization. The protein kinase AMPK, CK1α, MAP4K3 phosphorylates induces decreasing its ubiquitination. ubiquitination induced E3 ubiquitin ligase MDM2 UBR4 decreased deubiquitinase UCHL1 USP50. increased PIAS4-mediated SUMOylation methyltransferase PRMT5-mediated methylation, AP2-mediated lysosomal degradation. downregulated in human diseases like diabetes, hypertension, lung injury. In contrast, upregulates levels, enhancing cell susceptibility to Moreover, soluble exosomal facilitate infection into cells. this review, we summarize gene disease COVID-19. Understanding may help develop prevention treatment strategies ACE2-mediated

Язык: Английский

---

Identification of host dependency factors involved in SARS-CoV-2 replication organelle formation through proteomics and ultrastructural analysis

Journal of Virology, Год журнала: 2023, Номер 97(11)

Опубликована: Окт. 31, 2023

Remodeling of the cellular endomembrane system by viruses allows for efficient and coordinated replication viral genome in distinct subcellular compartments termed organelles. As a critical step life cycle, organelle formation is an attractive target therapeutic intervention, but factors central to this process are only partially understood. In study, we corroborate that two proteins, nsp3 nsp4, major drivers membrane remodeling SARS-CoV-2 infection. We further report number host cell interacting with these proteins supporting some them contributing organelle.

Язык: Английский

---

Insights into the Activation of Unfolded Protein Response Mechanism during Coronavirus Infection

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(5), С. 4286 - 4308

Опубликована: Май 5, 2024

Coronaviruses represent a significant class of viruses that affect both animals and humans. Their replication cycle is strongly associated with the endoplasmic reticulum (ER), which, upon virus invasion, triggers ER stress responses. The activation unfolded protein response (UPR) within infected cells performed from three transmembrane receptors, IRE1, PERK, ATF6, results in reduction production, boost ER’s ability to fold proteins properly, initiation ER-associated degradation (ERAD) remove misfolded or proteins. However, cases prolonged severe stress, UPR can also instigate apoptotic cell death inflammation. Herein, we discuss ER-triggered host responses after coronavirus infection, as well pharmaceutical targeting potential antiviral strategy.

Язык: Английский

---

Transmission of unfolded protein response—a regulator of disease progression, severity, and spread in virus infections

mBio, Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

ABSTRACT The unfolded protein response (UPR) is a cell-autonomous stress aimed at restoring homeostasis due to the accumulation of misfolded proteins in endoplasmic reticulum (ER). Viruses often hijack host cell machinery, leading an ER. UPR immediate infected this stress, aiming restore normal function by halting translation, degrading proteins, and activating signaling pathways that increase production molecular chaperones. cell-non-autonomous involves spreading signals from initially stressed cells neighboring unstressed lack stressor. Though viruses are known modulators UPR, recent advancements have highlighted plays critical role elucidating how local infections cause systemic effects, thereby contributing disease symptoms progression. Additionally, utilizing devised novel strategies establish pro-viral state, promoting virus spread. This review discusses examples broadened understanding progression looking beyond non-autonomous processes mechanistic details inducers, spreaders, receivers signals.

Язык: Английский

---

Highly Dynamic Cytoskeletal Networks Support Productive Viral Infection and Host Innate Immune Response Activation

Current Clinical Microbiology Reports, Год журнала: 2025, Номер 12(1)

Опубликована: Фев. 22, 2025

Язык: Английский

---

Clicking viruses—with chemistry toward mechanisms in infection

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Май 14, 2025

ABSTRACT Viruses subvert cells and evade host defense. They emerge unpredictably threaten humans livestock through their genetic phenotypic diversity. Despite more than 100 years since the discovery of viruses, molecular underpinnings virus infections are incompletely understood. The introduction new methodologies into field, such as that click chemistry some 10 ago, keeps uncovering facets viruses. Click uses bio-orthogonal reactions on chemical probes couples nucleic acids, proteins, lipids with tractable labels, fluorophores for single-cell single-molecule imaging, or biotin biochemical profiling infections. Its applications in single often achieve resolution provide important insights widely known phenomenon cell-to-cell infection variability. This review describes advances to unravel mechanisms a select set enveloped nonenveloped DNA RNA including adenovirus, herpesvirus, human immunodeficiency virus. It highlights recent breakthroughs viral DNA, RNA, protein, well host-derived lipid functions both live chemically fixed cells. discusses specific processes entry, uncoating, transcription, replication, packaging, assembly provides perspective explore cell biology, variability, genome organization particle.

Язык: Английский

---

Zika virus prM protein contains cholesterol binding motifs required for virus entry and assembly

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Ноя. 13, 2023

For successful infection of host cells and virion production, enveloped viruses, including Zika virus (ZIKV), extensively rely on cellular lipids. However, how protein-lipid interactions contribute to the viral life cycle remains unclear. Here, we employ a chemo-proteomics approach with bifunctional cholesterol probe show that is closely associated ZIKV structural protein prM. Bioinformatic analyses, reverse genetics alongside photoaffinity labeling assays, atomistic molecular dynamics simulations identified two functional binding motifs within prM transmembrane domain. Loss prM-cholesterol association has bipartite effect reducing entry leading assembly defects. We propose model in which membrane-resident M facilitates cholesterol-supported lipid exchange during endosomal and, together cholesterol, creates platform promoting assembly. In summary, identify role by mediating cholesterol-dependent manner.

Язык: Английский

---

The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2024, Номер 1870(5), С. 167193 - 167193

Опубликована: Апрель 21, 2024

Язык: Английский

---

AGR2: The Covert Driver and New Dawn of Hepatobiliary and Pancreatic Cancer Treatment

Biomolecules, Год журнала: 2024, Номер 14(7), С. 743 - 743

Опубликована: Июнь 23, 2024

The anterior gradient protein 2 (AGR2) plays a crucial role in facilitating the formation of disulfide bonds within endoplasmic reticulum (ER). Research suggests that AGR2 can function as an oncogene, with its heightened expression linked to advancement hepatobiliary and pancreatic cancers through invasion metastasis. Notably, not only serves pro-oncogenic agent but also downstream targeting protein, indirectly fostering cancer progression. This comprehensive review delves into established functions patterns AGR2, emphasizing pivotal progression, particularly malignancies. Furthermore, emerges potential prognostic marker promising target for immunotherapy, offering novel avenues treatment enhancing patient outcomes.

Язык: Английский

---