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PMID:15614436

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Citation

Zhang, JL, Zhao, WG, Wu, KL, Wang, K, Zhang, X, Gu, CF, Li, Y, Zhu, Y and Wu, JG (2005) Human hepatitis B virus X protein promotes cell proliferation and inhibits cell apoptosis through interacting with a serine protease Hepsin. Arch. Virol. 150:721-41

Abstract

The X protein of human hepatitis B virus (HBV) acts as an indirect transcriptional transactivator to regulate the expression of many viral and cellular genes as well as playing a critical role in the development of hepatocellular carcinoma. While the biological importance of HBx has been well established, the cellular and molecular bases of its function remain largely undefined. In this study, we isolated a new HBV field strain from a patient with chronic viral infection. The X protein encoded by this virus was used as a bait protein for screening a human liver cDNA library using a yeast two-hybrid system. Several cell proteins were identified as new HBx interacting partners, including a transmembrane serine protease, Hepsin. Direct interaction between HBx and Hepsin proteins was confirmed by in vitro and in vivo co-immunoprecipitation assays. HBx also co-localized with Hepsin in human cells as determined by confocal immunofluorescence microscopy. The interaction between HBx and Hepsin protein appeared to play a role in both promoting cell proliferation and blocking apoptosis in human liver tumor cell and normal liver cell lines. In addition, the complex of HBx and Hepsin promoted the expression of HBeAg in Hep G2.2.1.5 cells indicating that the association of these two proteins stimulated viral replication.

Links

PubMed Online version:10.1007/s00705-004-0446-0

Keywords

Apoptosis/drug effects; Base Sequence; Carcinoma, Hepatocellular/pathology; Cell Division/drug effects; Cell Line; Cell Line, Tumor; DNA Primers; Hepatitis B Antigens/metabolism; Hepatitis B Antigens/pharmacology; Humans; Liver; Liver Neoplasms; Membrane Proteins/metabolism; Serine Endopeptidases/metabolism; Trans-Activators/metabolism; Trans-Activators/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:HEPS

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q7TDY3

F

Seeded From UniProt

complete

HUMAN:HEPS

colocalizes_with

GO:0031965: nuclear membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HEPS

involved_in

GO:2000347: positive regulation of hepatocyte proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HEPS

involved_in

GO:0043923: positive regulation by host of viral transcription

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:Q89714)

Seeded From UniProt

complete

HUMAN:HEPS

involved_in

GO:0043066: negative regulation of apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CATB

located_in

GO:0048471: perinuclear region of cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HBV:Q7TDY3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P05981

F

Seeded From UniProt

complete

HBV:Q7TDY3

colocalizes_with

GO:0044200: host cell nuclear membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000002)

Seeded From UniProt

complete

HBV:Q7TDY3

involved_in

GO:2000347: positive regulation of hepatocyte proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000002)

Seeded From UniProt

complete

HBV:Q7TDY3

involved_in

GO:0050434: positive regulation of viral transcription

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:Q89714)

Seeded From UniProt

complete

HBV:Q7TDY3

involved_in

GO:0043066: negative regulation of apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CATB

part_of

GO:0048471: perinuclear region of cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

See also

References

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