Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and inhibits apoptosis in Huh7 hepatoma cells

Jiadong Wang; Wenyan Tong; Xiaonan Zhang; Li Chen; Zhigang Yi; Tingting Pan; Yunwen Hu; Li Xiang; Zhenghong Yuan

doi:10.1016/j.febslet.2006.07.002

Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and inhibits apoptosis in Huh7 hepatoma cells

Jiadong Wang, Wenyan Tong, Xiaonan Zhang, Li Chen, Zhigang Yi, Tingting Pan, Yunwen Hu, Li Xiang, Zhenghong Yuan

Research output: Contribution to journal › Review article › peer-review

57 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	4392-4400
Number of pages	9
Journal	FEBS Letters
Volume	580
Issue number	18
DOIs	https://doi.org/10.1016/j.febslet.2006.07.002
Publication status	Published - 7 Aug 2006
Externally published	Yes

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@article{72a00580fe584929b52e606c694f262d,

title = "Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and inhibits apoptosis in Huh7 hepatoma cells",

abstract = "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.",

keywords = "Animals, Apoptosis, Binding Sites, COS Cells, Carcinoma, Hepatocellular, Cell Line, Tumor, Chlorocebus aethiops, Endoplasmic Reticulum/chemistry, Humans, Immunoprecipitation, Liver/virology, Liver Neoplasms, Mitochondria/chemistry, Protein Structure, Tertiary, RNA Interference, Tacrolimus Binding Proteins/analysis, Two-Hybrid System Techniques, Viral Nonstructural Proteins/analysis",

author = "Jiadong Wang and Wenyan Tong and Xiaonan Zhang and Li Chen and Zhigang Yi and Tingting Pan and Yunwen Hu and Li Xiang and Zhenghong Yuan",

year = "2006",

month = aug,

day = "7",

doi = "10.1016/j.febslet.2006.07.002",

language = "English",

volume = "580",

pages = "4392--4400",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Wiley-Blackwell",

number = "18",

}

TY - JOUR

T1 - Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and inhibits apoptosis in Huh7 hepatoma cells

AU - Wang, Jiadong

AU - Tong, Wenyan

AU - Zhang, Xiaonan

AU - Chen, Li

AU - Yi, Zhigang

AU - Pan, Tingting

AU - Hu, Yunwen

AU - Xiang, Li

AU - Yuan, Zhenghong

PY - 2006/8/7

Y1 - 2006/8/7

N2 - 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.

AB - 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.

KW - Animals

KW - Apoptosis

KW - Binding Sites

KW - COS Cells

KW - Carcinoma, Hepatocellular

KW - Cell Line, Tumor

KW - Chlorocebus aethiops

KW - Endoplasmic Reticulum/chemistry

KW - Humans

KW - Immunoprecipitation

KW - Liver/virology

KW - Liver Neoplasms

KW - Mitochondria/chemistry

KW - Protein Structure, Tertiary

KW - RNA Interference

KW - Tacrolimus Binding Proteins/analysis

KW - Two-Hybrid System Techniques

KW - Viral Nonstructural Proteins/analysis

U2 - 10.1016/j.febslet.2006.07.002

DO - 10.1016/j.febslet.2006.07.002

M3 - Review article

C2 - 16844119

SN - 0014-5793

VL - 580

SP - 4392

EP - 4400

JO - FEBS Letters

JF - FEBS Letters

IS - 18

ER -

Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and inhibits apoptosis in Huh7 hepatoma cells

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