The core protein of hepatitis C virus is imported into the nucleus by transport receptor Kap123p but inhibits Kap121p-dependent nuclear import of yeast AP1-like transcription factor in yeast cells.
The core protein of hepatitis C virus (HCV) is a major component of the viral nucleocapsid. The HCV core protein includes nuclear localization signal-like sequences and has various effects on cellular metabolism, playing roles, for example, in the regulation of transcription, apoptosis, and transformation. To examine the possibility of an effect of the core protein on nucleocytoplasmic transport, we used the yeast Saccharomyces cerevisiae as a model system. The core protein (p23) is processed to p21 and is localized in both the cytoplasm and nucleus in yeast cells, similar to that observed in mammalian cells in several cases. The nuclear import of the core protein requires the activity of small GTPase Ran/Gsp1p and is mediated by Kap123p in yeast cells. When the core protein was expressed in yeast cells, the import of the yeast AP1-like transcription factor Yap1p into the nucleus was inhibited. Experiments in vitro involving Kap121p, also known as Pse1p, a receptor for the nuclear import of Yap1p, indicated that the amount of Yap1p bound to Kap121p was reduced in the presence of core protein. These results suggest that the HCV core protein affects cellular metabolism by disturbing transport of proteins to the nucleus.
Isoyama
Takeshi
T
Department of Microbiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kuge
Shusuke
S
Nomoto
Akio
A
D021581:Active Transport, Cell Nucleus; D000483:Alleles; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D049452:Green Fluorescent Proteins; D015151:Immunoblotting; D007700:Kinetics; D008164:Luminescent Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D008856:Microscopy, Fluorescence; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D013696:Temperature; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014758:Viral Core Proteins / Q000737:chemistry*; D028961:beta Karyopherins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C080324:GSP1 protein, S cerevisiae; C109173:Kap123 protein, S cerevisiae; D008164:Luminescent Proteins; D026901:Membrane Transport Proteins; D009687:Nuclear Proteins; C483822:PSE1 protein, S cerevisiae; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014758:Viral Core Proteins; C086677:YAP1 protein, S cerevisiae; D028961:beta Karyopherins; C069130:nucleocapsid protein, Hepatitis C virus; D049452:Green Fluorescent Proteins; D020558:GTP Phosphohydrolases; D020559:Monomeric GTP-Binding Proteins