Reactome | Interaction of ISG15 with NEDD4 and inhibition of Ebola virus budding

Interaction of ISG15 with NEDD4 and inhibition of Ebola virus budding

Stable Identifier

R-HSA-1169399

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Interaction of ISG15 with NEDD4 and inhibition of Ebola virus budding

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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
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
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, 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