Association of mumps virus V protein with RACK1 results in dissociation of STAT-1 from the alpha interferon receptor complex.
It has been reported that mumps virus protein V or the C-terminal Cys-rich region of protein V (Vsp) is associated with blocking of the interferon (IFN) signal transduction pathway through a decrease in STAT-1 production. The intracellular target of the V protein was investigated by using a two-hybrid screening system with Vsp as bait. Full-length V protein and Vsp were able to bind to RACK1, and the interaction did not require two WD domains, WD1 and WD2, in RACK1. A significant interaction between V protein and RACK1 was also demonstrated in cells persistently infected with mumps virus (FLMT cells), and the formation of the complex was not affected by treatment with IFN. On the other hand, in uninfected cells, STAT-1 was associated with the long form of the beta subunit of the alpha IFN receptor, and this association was mediated by the function of RACK1 as an adaptor protein. Immunoprecipitation and glutathione S-transferase pull-down experiments revealed that the association of RACK1 or mumps virus V protein with the IFN receptor was undetectable in mumps virus-infected cells. Furthermore, RACK1 interacted with mumps virus V protein with a higher affinity than STAT-1 did. Therefore, it is suggested that mumps virus V protein has the ability to interact strongly with RACK1 and consequently to bring about the disruption of the complex formed from STAT-1, RACK1, and the IFN receptor.
Kubota
Toru
T
Department of Microbiology, School of Medicine, Sapporo Medical University, South 1 West 17, Chou-ku, Sapporo 060-8556, Hokkaido, Japan.
Yokosawa
Noriko
N
Yokota
Shin-ichi
S
Fujii
Nobuhiro
N
D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D009109:Mumps virus / Q000502:physiology*; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D053633:Receptor, Interferon alpha-beta; D000075370:Receptors for Activated C Kinase; D017471:Receptors, Interferon / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D010455:Peptides; D000075370:Receptors for Activated C Kinase; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014764:Viral Proteins; C070301:peptide I; D053633:Receptor, Interferon alpha-beta