Stearoylation cycle regulates the cell surface distribution of the PCP protein Vangl2

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(29)

Published: July 10, 2024

Defects in planar cell polarity (PCP) have been implicated diverse human pathologies. Vangl2 is one of the core PCP components crucial for signaling. Dysregulation has associated with severe neural tube defects and cancers. However, how protein regulated at posttranslational level not well understood. Using chemical reporters fatty acylation biochemical validation, here we present that subcellular localization by a reversible S-stearoylation cycle. The dynamic process mainly acyltransferase ZDHHC9 deacylase acyl-protein thioesterase 1 (APT1). stearoylation-deficient mutant shows decreased plasma membrane localization, resulting disruption establishment during migration. Genetically or pharmacologically inhibiting phenocopies effects stearoylation loss Vangl2. In addition, enhances activation oncogenic Yes-associated (YAP), serine-threonine kinase AKT, extracellular signal-regulated (ERK) signaling promotes breast cancer growth HRas G12V (HRas V12 )-induced transformation. Our results reveal regulation mechanism Vangl2, provide mechanistic insight into acid metabolism regulate tumorigenesis lipidation.

Language: Английский

---

bcIRF5 activates bcTBK1 phosphorylation to enhance PANoptosis during GCRV infection

Fish & Shellfish Immunology, Journal Year: 2024, Volume and Issue: 154, P. 109968 - 109968

Published: Oct. 15, 2024

Language: Английский

---

Nasal microbiota homeostasis regulates host anti-influenza immunity via the IFN and autophagy pathways in beagles

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Background The respiratory tract houses a specialized microbial ecosystem, and despite the close anatomical physiological ties between oral, upper respiratory, lower tracts, there is substantial discrepancy in quantity, spanning multiple orders of magnitude. potential for commensal bacteria to prevent infection lies their ability regulate innate adaptive host immune responses. Influenza virus predominantly targets replicates within epithelial cells both tracts. Given this, we hypothesize that nasal-lung-microbe cross-talk plays crucial role influencing influenza susceptibility. In this study, investigated viral presence, gene expression profiles host, nasal lung microbiota beagle dog model with antibiotic-induced dysbiosis during infection. Results using 16S rRNA sequencing, combined comparative anatomy, transcriptomics histological examination, influenza-infected beagles dysbiosis. Our data showed microbiome exacerbates influenza-induced disease barrier disruption, impairs antiviral responses cavity lung. Moreover, dysregulation worsens disturbance microbiota. Further, identified one strain Lactobacillus plantarum significant effect, which exerted by activating IFN pathway modulating impaired autophagy flux induced virus. collectively indicate connection microbiomes different ecological niches regions. This significantly influences subsequent host-microbe cross-talk, was associated an increased susceptibility influenza. Conclusions investigation reveals not only increases but also contributes exacerbation dysregulation. intricate relationship extends composition, demonstrating correlations critical factors such as responses, inflammation thresholds, mucosal integrity. Together, these findings underscore impact on overall outcome infections.

Language: Английский

---

E3 ligase ASB3 downregulates antiviral innate immunity by targeting MAVS for ubiquitin-proteasomal degradation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 10, 2023

ABSTRACT E3 ubiquitin ligases are very important to regulate antiviral immunity during viral infection. Here, we discovered that Ankyrin repeat and SOCS box-containing protein 3 (ASB3), an ligase, upregulated in the presence of RNA viruses, particularly Influenza A virus (IAV). Notably, overexpression ASB3 inhibits type I IFN (IFN-I) responses induced by Sendai (SeV) H9N2, ablation restores SeV H9N2 infection-mediated transcription IFN-β its downstream interferon-stimulated genes (ISGs). Interestingly, animals lacking showed a decreased susceptibility PR8 infections. Mechanistically, interacts with MAVS directly mediates K48-linked polyubiquitination degradation at K297, thereby inhibiting phosphorylation levels TBK1 IRF3, downregulating signaling. These findings establish as critical negative regulator controlling activation signaling describe novel function has not been previously reported. IMPORTANCE IAV is significant zoonotic pathogen causes infections respiratory system. Hosts have evolved multiple strategies defend against However, all host proteins play active defense role. In this study, found ligase regulates manipulating stability. Briefly, degrades MAVS, promoting replication. contrast, deletion expression, upregulating IFN-I responses. Additional research revealed resulting being degraded via ubiquitin-proteasome pathway. reveal, for first time, mechanism which negatively provides potential target anti-IAV drug development.

Language: Английский

---