Hepatitis C virus ARFP/F protein interacts with cellular MM-1 protein and enhances the gene trans-activation activity of c-Myc.
The ARFP/F protein is synthesized from the +1 reading frame of the hepatitis C virus (HCV) core protein gene. The function of this protein remains unknown. To study the function of the HCV ARFP/F protein, we have conducted the yeast two-hybrid screening experiment to identify cellular proteins that may interact with the ARFP/F protein. MM-1, a c-Myc interacting protein, was found to interact with HCV ARFP/F protein in this experiment. The physical interaction between ARFP/F and MM-1 proteins was further confirmed by the GST pull-down assay, the co-immunoprecipitation assay and confocal microscopy. As MM-1 can inhibit the gene transactivation activity of c-Myc, we have conducted further analysis to examine the possible effect of the ARFP/F protein on c-Myc. Our results indicate that the HCV ARFP/F protein can enhance the gene trans-activation activity of c-Myc, apparently by antagonizing the inhibitory effect of MM-1. The ability of the ARFP/F protein to enhance the activity of c-Myc raises the possibility that ARFP/F protein might play a role in hepatocellular transformation in HCV patients.
Ma
Hsin-Chieh
HC
Graduate Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
Lin
Ta-Wei
TW
Li
Huichun
H
Iguchi-Ariga
Sanae M M
SM
Ariga
Hiroyoshi
H
Chuang
Yu-Li
YL
Ou
Jing-Hsiung
JH
Lo
Shih-Yen
SY
D016174:Hepacivirus / Q000737:chemistry*; D006801:Humans; D011485:Protein Binding; D025941:Protein Interaction Mapping; D016271:Proto-Oncogene Proteins c-myc / Q000819:agonists* / Q000502:physiology; D012097:Repressor Proteins / Q000378:metabolism*; D015533:Transcriptional Activation; D014758:Viral Core Proteins / Q000502:physiology*
C489427:MYC protein, human; C115636:PFDN5 protein, human; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus