Interaction of ISG15 with NEDD4 and inhibition of Ebola virus budding

Stable Identifier
R-HSA-1169399
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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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
18287095 ISG15 inhibits Nedd4 ubiquitin E3 activity and enhances the innate antiviral response

Malakhova, OA, Zhang, DE

J Biol Chem 2008
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

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

J Virol 2003
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, Brown, ME, Wang, G, Huibregtse, J, Hayes, FP

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, Pitha-Rowe, PM, Harty, RN

Proc Natl Acad Sci U S A 2008
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