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Apoptosis

, Volume 12, Issue 10, pp 1827–1836 | Cite as

The hepatitis B virus protein MHBs(t) sensitizes hepatoma cells to TRAIL-induced apoptosis through ERK2

  • Xiaohong Liang
  • Juan Du
  • Yugang Liu
  • Min Cui
  • Chunhong Ma
  • Lihui Han
  • Zhonghua Qu
  • Zhiyong Zhang
  • Zhaohui Sun
  • Lining Zhang
  • Youhai H. Chen
  • Wensheng Sun
Original Paper

Abstract

The TNF-related apoptosis-inducing ligand (TRAIL) has recently been implicated in the death of hepatocytes under infectious but not normal conditions. Infectious agents, such as hepatitis B virus (HBV), may play important roles in regulating the sensitivity of hepatocytes to TRAIL. Our previous studies showed that HBx, a protein encoded by the HBV genome, enhanced TRAIL-induced apoptosis through upregulating Bax. We report here that another HBV protein called MHBs(t) (C-terminally truncated middle hepatitis B surface protein) is also a potent regulator of TRAIL-induced apoptosis. Overexpressing MHBs(t) in hepatoma cells enhanced TRAIL-induced apoptosis. Mechanistic studies reveal that MHBs(t) had no effect on Bax or TRAIL receptor expression or procaspase-8 activation, but selectively enhanced the activation of ERK2 (extracellular signal-regulated kinase 2) and the degradation of procaspases-3 and 9. ERK2 activation is required for the MHBs(t) effect because ERK2 inhibition by its inhibitor PD98059 significantly reversed TRAIL-induced apoptosis of MHBs(t)-transfected cells. These results establish that unlike HBx, MHBs(t) enhances TRAIL-induced hepatocyte apoptosis through a novel mechanism that involves ERK2. Therefore, manipulating the ERK2 signaling pathway may provide new therapeutic opportunities to contain hepatic cell death during HBV infection.

Keywords

Apoptosis TNF-related apoptosis inducing ligand Hepatitis B virus Truncated middle hepatitis B surface protein ERK2 

Notes

Acknowledgements

This work was supported by grants from the Natural Science Foundation of China (No. 30128023, 30440040, and 30371342).

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Xiaohong Liang
    • 1
  • Juan Du
    • 1
  • Yugang Liu
    • 2
  • Min Cui
    • 3
  • Chunhong Ma
    • 1
  • Lihui Han
    • 1
  • Zhonghua Qu
    • 1
  • Zhiyong Zhang
    • 1
  • Zhaohui Sun
    • 1
  • Lining Zhang
    • 1
  • Youhai H. Chen
    • 4
  • Wensheng Sun
    • 1
  1. 1.Institute of Immunology, School of MedicineShandong UniversityJinanPeople’s Republic of China
  2. 2.Institute of Pathophysiology, School of MedicineShandong UniversityJinanPeople’s Republic of China
  3. 3.Institute of Physiology, School of MedicineShandong UniversityJinanPeople’s Republic of China
  4. 4.614 BRB-II/III, Department of Pathology and Laboratory MedicineUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

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