The Marburg Virus VP24 Protein Interacts with Keap1 to Activate the Cytoprotective Antioxidant Response Pathway

Kelch-like ECH-associated protein 1 (Keap1) is a ubiquitin E3 ligase specificity factor that targets transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) for ubiquitination and degradation. Disrupting Keap1-Nrf2 interaction stabilizes Nrf2, resulting in Nrf2 nuclear accumulation,...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Cell reports (Cambridge) Ročník 6; číslo 6; s. 1017 - 1025
Hlavní autoři: Edwards, Megan R., Johnson, Britney, Mire, Chad E., Xu, Wei, Shabman, Reed S., Speller, Lauren N., Leung, Daisy W., Geisbert, Thomas W., Amarasinghe, Gaya K., Basler, Christopher F.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Elsevier 01.03.2014
Témata:
Animals
Antioxidants - metabolism
Cytoprotection
Gene Expression
HEK293 Cells
Humans
Intracellular Signaling Peptides and Proteins - metabolism
Kelch-Like ECH-Associated Protein 1
Marburg virus
Marburg Virus Disease - metabolism
Marburg Virus Disease - virology
Marburgvirus - genetics
Marburgvirus - metabolism
Models, Molecular
NF-E2-Related Factor 2 - genetics
NF-E2-Related Factor 2 - metabolism
Oxidative Stress - physiology
Protein Binding
Protein Structure, Tertiary
Substrate Specificity
Transfection
Viral Proteins - biosynthesis
Viral Proteins - genetics
Viral Proteins - metabolism
ISSN:2211-1247, 2211-1247
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:Kelch-like ECH-associated protein 1 (Keap1) is a ubiquitin E3 ligase specificity factor that targets transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) for ubiquitination and degradation. Disrupting Keap1-Nrf2 interaction stabilizes Nrf2, resulting in Nrf2 nuclear accumulation, binding to antioxidant response elements (AREs), and transcription of cytoprotective genes. Marburg virus (MARV) is a zoonotic pathogen that likely uses bats as reservoir hosts. We demonstrate that MARV protein VP24 (mVP24) binds the Kelch domain of either human or bat Keap1. This binding is of high affinity and 1:1 stoichiometry and activates Nrf2. Modeling based on the Zaire ebolavirus (EBOV) VP24 (eVP24) structure identified in mVP24 an acidic loop (K-loop) critical for Keap1 interaction. Transfer of the K-loop to eVP24, which otherwise does not bind Keap1, confers Keap1 binding and Nrf2 activation, and infection by MARV, but not EBOV, activates ARE gene expression. Therefore, MARV targets Keap1 to activate Nrf2-induced cytoprotective responses during infection.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Current Address: J. Craig Venter Institute, Rockville, Maryland, USA 20850
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2014.01.043