Mitochondrially associated hepatitis B virus X protein constitutively activates transcription factors STAT-3 and NF-kappa B via oxidative stress

Molecular and Cellular Biology
G WarisA Siddiqui

Abstract

The hepatitis B virus X protein (HBx) plays essential roles in viral replication and the generation of hepatocellular carcinoma. In spite of a large number of suggestive cellular targets and functions, a clear picture of its mechanism(s) of action has remained elusive. In this report, we continue to characterize its recently described mitochondrial association and further examine its impact on mitochondrial functions. HBx was previously shown to bind to a voltage-dependent anion channel (VDAC3) and alter the mitochondrial transmembrane potential (Delta Psi(m)). Here we show that, as a consequence of association with mitochondria, HBx constitutively induces activation of transcription factors, which include STAT-3 and NF-kappa B. This induction of activation was sensitive to the antioxidants N-acetyl L-cysteine and pyrrolidine dithiocarbamate, as well as to overexpression of Mn-superoxide dismutase. These results therefore implicate a potential role of reactive oxygen species (ROS) in a process that ultimately leads to the activation of STAT-3 and NF-kappa B. Evidence is also presented for the HBx-induced generation of ROS. The ability of HBx to induce the activation of STAT-3 and NF-kappa B was demonstrated by mobility shift an...Continue Reading

References

Dec 1, 1992·Free Radical Biology & Medicine·F Müller
Jan 1, 1990·Free Radical Biology & Medicine·Y Sun
Mar 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J S Twu, W S Robinson
Oct 15, 1986·Cancer·R CorrocherG De Sandre
Feb 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·M A SellsG Acs
Apr 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·A SiddiquiJ Mapoles
Nov 21, 1995·Proceedings of the National Academy of Sciences of the United States of America·J Benn, R J Schneider
Apr 25, 1995·Proceedings of the National Academy of Sciences of the United States of America·J S Williams, O M Andrisani
Feb 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·I QadriA Siddiqui
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·J Benn, R J Schneider
Mar 1, 1994·Journal of Virology·F ZoulimC Seeger
Mar 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·X W WangC C Harris
May 28, 1996·Proceedings of the National Academy of Sciences of the United States of America·V KumarR Kumar
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·I QadriA Siddiqui
Jan 1, 1996·Free Radical Biology & Medicine·K B Schwarz
Aug 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·F Su, R J Schneider
Sep 12, 1997·Science·J E Darnell
Oct 29, 1997·Molecular and Cellular Biology·N P Klein, R J Schneider
Jan 7, 1998·Journal of Virology·S A BeckerB L Slagle
Mar 6, 1998·Molecular and Cellular Biology·I HavivY Shaul
Aug 28, 1998·Science·D R Green, J C Reed
Sep 17, 1998·The Journal of Biological Chemistry·Y H Lee, Y Yun
Jun 11, 1999·The Journal of Biological Chemistry·M CarballoF Sobrino
Sep 16, 1999·The EMBO Journal·N P KleinR J Schneider
Feb 7, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S SchoonbroodtJ Piette

❮ Previous
Next ❯

Citations

Aug 29, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Michael Nassal
May 8, 2003·Journal of Biosciences·G Waris, A Siddiqui
Nov 27, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Wonchung LimHyeseong Cho
Oct 12, 2011·Archives of Gynecology and Obstetrics·Guiqin BaiFengping Fu
Feb 9, 2007·Journal of Gastroenterology·Yutaka Sasaki
Jul 3, 2008·Apoptosis : an International Journal on Programmed Cell Death·Yinna WeiPingping Shen
Nov 2, 2012·Cancer Metastasis Reviews·Mausumi BharadwajShowket Hussain
Apr 11, 2003·Virus Research·Milena PantevaShahid Jameel
Aug 27, 2005·Mitochondrion·Kyung-Won Huh, Aleem Siddiqui
Jan 25, 2011·The British Journal of Nutrition·Sirio FiorinoPietro Andreone
Sep 13, 2002·Journal of Viral Hepatitis·Naazneen MoollaPatrick Arbuthnot
Aug 7, 2004·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Kristen MillerStephen J Polyak
Jul 18, 2012·Antioxidants & Redox Signaling·Roberto P GarofaloAntonella Casola
May 15, 2013·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Jing ZhaoKai Wang
Feb 2, 2010·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Liu HongQing Li
May 9, 2006·Journal of Gastroenterology and Hepatology·Xiao Zhong WangZhi Xin Chen
Aug 8, 2006·Postgraduate Medical Journal·N H ParkY-H Chung
Mar 6, 2003·The Journal of Clinical Investigation·David A HildemanPhilippa Marrack
May 13, 2006·Journal of Carcinogenesis·Gulam Waris, Haseeb Ahsan
Dec 4, 2012·Viruses·Siddhartha RawatMichael J Bouchard
Feb 6, 2009·World Journal of Gastroenterology : WJG·Isabel Fabregat
Dec 25, 2010·World Journal of Gastroenterology : WJG·Hye-Lin HaDae-Yeul Yu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.