Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and inhibits apoptosis in Huh7 hepatoma cells.
Hepatitis C virus non-structural protein NS5A plays an important role in viral replication and various cellular events. To gain further insight into the function of NS5A, we screened a human fetal liver cDNA library for its interacting proteins using the yeast two-hybrid system. FKBP38, a 38 kDa immunosuppressant FK506-binding protein, was identified and its interaction with NS5A was confirmed by both in vitro and in vivo. The interaction was mapped to the amino acids 148-236 of NS5A containing a BH domain (Bcl-2 homology domain). Besides, both NS5A and FKBP38 were found to localize in mitochondria and endoplasmic reticulum. Moreover, NS5A stably expressing Huh7 hepatoma cells showed more resistance to apoptosis and such inhibition of apoptosis could specifically be abrogated by depletion of FKBP38 using RNA interference. These results indicate that HCV NS5A inhibits apoptosis through interaction with FKBP38.
Wang
Jiadong
J
Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Institutes of Medical Microbiology and Biomedical Sciences, Fudan University, P.O. Box 228, 138 Yi Xue Yuan Road, Shanghai 200032, PR China.
Tong
Wenyan
W
Zhang
Xiaonan
X
Chen
Li
L
Yi
Zhigang
Z
Pan
Tingting
T
Hu
Yunwen
Y
Xiang
Li
L
Yuan
Zhenghong
Z
D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D019556:COS Cells; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000821:virology; D006801:Humans; D047468:Immunoprecipitation; D008099:Liver / Q000821:virology*; D008113:Liver Neoplasms; D008928:Mitochondria / Q000737:chemistry / Q000821:virology; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D022021:Tacrolimus Binding Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D017361:Viral Nonstructural Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase
D022021:Tacrolimus Binding Proteins; D017361:Viral Nonstructural Proteins; C471205:FKBP8 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase