Interaction of ISG15 with NEDD4 and inhibition of Ebola virus budding

Stable Identifier
Reaction [binding]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Ebola virus VP40 virus-like particles (VLPs) requires the interaction of overlapping L-domains in the VP40 protein with host NEDD4 protein for efficient budding. Mono-ubiquitination of VP40 mediated by the NEDD4 E3 ligase is thought to be required for virus budding and release. ISG15 interacts with NEDD4 and inhibits the transfer of ubiquitin from the E2 enzyme to NEDD4. This prevents NEDD4-mediated ubiquitination of Ebola virus VP40 which is required for virion release.
Literature References
PubMed ID Title Journal Year
12525615 Overlapping motifs (PTAP and PPEY) within the Ebola virus VP40 protein function independently as late budding domains: involvement of host proteins TSG101 and VPS-4

Wright, NT, Licata, JM, Harty, RN, Han, Z, Simpson-Holley, M, Paragas, J

J Virol 2003
18287095 ISG15 inhibits Nedd4 ubiquitin E3 activity and enhances the innate antiviral response

Malakhova, OA, Zhang, DE

J Biol Chem 2008
11095724 A PPxY motif within the VP40 protein of Ebola virus interacts physically and functionally with a ubiquitin ligase: implications for filovirus budding

Harty, RN, Wang, G, Hayes, FP, Huibregtse, J, Brown, ME

Proc Natl Acad Sci U S A 2000
18305167 ISG15 inhibits Ebola VP40 VLP budding in an L-domain-dependent manner by blocking Nedd4 ligase activity

Okumura, A, Harty, RN, Pitha-Rowe, PM

Proc Natl Acad Sci U S A 2008
Orthologous Events
Cite Us!