دورية أكاديمية
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Hippo signaling pathway regulates Ebola virus transcription and egress.

التفاصيل البيبلوغرافية
العنوان: Hippo signaling pathway regulates Ebola virus transcription and egress.
المؤلفون: Liang J; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA, 19104, USA., Djurkovic MA; Host-Pathogen Interactions, Texas Biomedical Research Institute, 8715 W. Military Drive, San Antonio, TX, 78227, USA., Leavitt CG; Host-Pathogen Interactions, Texas Biomedical Research Institute, 8715 W. Military Drive, San Antonio, TX, 78227, USA., Shtanko O; Host-Pathogen Interactions, Texas Biomedical Research Institute, 8715 W. Military Drive, San Antonio, TX, 78227, USA. oshtanko@txbiomed.org., Harty RN; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA, 19104, USA. rharty@vet.upenn.edu.
المصدر: Nature communications [Nat Commun] 2024 Aug 13; Vol. 15 (1), pp. 6953. Date of Electronic Publication: 2024 Aug 13.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Protein Serine-Threonine Kinases*/metabolism , Protein Serine-Threonine Kinases*/genetics , Hippo Signaling Pathway* , Signal Transduction* , Ebolavirus*/physiology , Ebolavirus*/genetics , Ebolavirus*/metabolism , Virus Release* , Transcription Factors*/metabolism , Transcription Factors*/genetics , Transcription, Genetic*, Humans ; Phosphorylation ; HEK293 Cells ; Tumor Suppressor Proteins/metabolism ; Tumor Suppressor Proteins/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Adaptor Proteins, Signal Transducing/genetics ; YAP-Signaling Proteins/metabolism ; Viral Matrix Proteins/metabolism ; Viral Matrix Proteins/genetics ; Hemorrhagic Fever, Ebola/virology ; Hemorrhagic Fever, Ebola/metabolism ; Host-Pathogen Interactions ; Cell Cycle Proteins/metabolism ; Cell Cycle Proteins/genetics
مستخلص: Filovirus-host interactions play important roles in all stages of the virus lifecycle. Here, we identify LATS1/2 kinases and YAP, key components of the Hippo pathway, as critical regulators of EBOV transcription and egress. Specifically, we find that when YAP is phosphorylated by LATS1/2, it localizes to the cytoplasm (Hippo "ON") where it sequesters VP40 to prevent egress. In contrast, when the Hippo pathway is "OFF", unphosphorylated YAP translocates to the nucleus where it transcriptionally activates host genes and promotes viral egress. Our data reveal that LATS2 indirectly modulates filoviral VP40-mediated egress through phosphorylation of AMOTp130, a positive regulator of viral egress, but more surprisingly that LATS1/2 kinases directly modulate EBOV transcription by phosphorylating VP30, an essential regulator of viral transcription. In sum, our findings highlight the potential to exploit the Hippo pathway/filovirus axis for the development of host-oriented countermeasures targeting EBOV and related filoviruses.
(© 2024. The Author(s).)
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معلومات مُعتمدة: AI151717 U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID); AI153815 U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID); AI139392 U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID); AI154336 U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID); R21 AI151717 United States AI NIAID NIH HHS; R21 AI139392 United States AI NIAID NIH HHS; R21 AI153815 United States AI NIAID NIH HHS; AI138052 U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID); R21 AI138052 United States AI NIAID NIH HHS; R21 AI154336 United States AI NIAID NIH HHS
المشرفين على المادة: EC 2.7.11.1 (Protein Serine-Threonine Kinases)
EC 2.7.1.- (LATS1 protein, human)
0 (Transcription Factors)
EC 2.7.1.11 (LATS2 protein, human)
0 (Tumor Suppressor Proteins)
0 (Adaptor Proteins, Signal Transducing)
0 (YAP-Signaling Proteins)
0 (Viral Matrix Proteins)
0 (VP40 protein, virus)
0 (YAP1 protein, human)
0 (Cell Cycle Proteins)
تواريخ الأحداث: Date Created: 20240813 Date Completed: 20240813 Latest Revision: 20240816
رمز التحديث: 20240817
مُعرف محوري في PubMed: PMC11322314
DOI: 10.1038/s41467-024-51356-z
PMID: 39138205
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-024-51356-z