Replication-initiator protein (UL9) of the herpes simplex virus 1 binds NFB42 and is degraded via the ubiquitin-proteasome pathway.
The ubiquitin-proteasome pathway plays a critical role in the degradation of short-lived and regulatory proteins in a variety of cellular processes. The F-box proteins are part of the ubiquitin-ligase complexes, which mediate ubiquitination and proteasome-dependent degradation of phosphorylated proteins. We previously identified NFB42, an F-box protein that is highly enriched in the nervous system, as a binding partner for the herpes simplex virus 1 UL9 protein, the viral replication-initiator protein, in a yeast two-hybrid screen. In the present work, we find that coexpression of NFB42 and UL9 genes in 293T cells leads to a significant decrease in the level of UL9 protein. Treatment with the 26S-proteasome inhibitor MG132 restores the UL9 protein to normal levels. We have observed also that the UL9 protein is polyubiquitinated in vivo and that the interaction between NFB42 and the UL9 protein is dependent upon phosphorylation of the UL9 protein. These results suggest that the interaction of the UL9 protein with NFB42 results in its polyubiquitination and subsequent degradation by the 26S proteasome. They suggest further a mechanism by which latency of herpes simplex virus 1 can be established in neuronal cells.
Eom
Chi-Yong
CY
Department of Biochemistry, Beckman Center, Stanford University School of Medicine, Stanford, CA 94305-5307, USA.
Lehman
I Robert
IR
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D044783:F-Box Proteins; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; C485508:FBXO2 protein, human; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D025801:Ubiquitin; D014764:Viral Proteins; C064565:UL9 protein, Human herpesvirus 1; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease