| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 41, 38847-38854, October 11, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Genetics and Microbiology, University
Medical Centre, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland
The hepatitis B virus X protein (HBx) is
essential for viral infection and strongly interferes with cell growth
and viability in culture. These activities involve interaction of HBx
with the DDB1 subunit of UV-damaged DNA-binding factor UV-DDB. UV-DDB
consists of DDB1 and a DDB2 subunit that mediates nuclear import and
has recognized functions in DNA repair and E2F1-mediated transcription. Here we show that HBx retains DDB1-binding-dependent cytotoxic activities when engineered to accumulate in the nucleus but not when
excluded from the nucleus. Nuclear localization of HBx does not require
binding to DDB1 and remains unaffected by ectopically expressed UV-DDB
subunits, indicating that HBx reaches the nuclear compartment
independently of UV-DDB. Unexpectedly, HBx appears to largely exist in
association with DDB1 and is in direct competition with DDB2 for
binding to DDB1. Hence, HBx-mediated cell death can be relieved by
increased levels of DDB2, an effect that is not observed with a
naturally occurring mutant of DDB2 that lacks DDB1-binding activity.
These findings indicate that HBx acts through a pathway that involves a
DDB2-independent nuclear function of DDB1 and that this activity will
depend on the relative concentration of DDB1 and DDB2 in cells.
Hepatitis B Virus X Protein Associated with UV-DDB1 Induces Cell
Death in the Nucleus and Is Functionally Antagonized by UV-DDB2*
,
*
This work was supported in part by a grant (31-49`792.96)
from the Swiss National Science Foundation (to M. S.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported by the Geneva Cancer League.
§
A recipient of a Roche Research Foundation fellowship and a
Novartis Research Foundation fellowship.
¶
To whom correspondence should be addressed. Tel.:
41-22-702-5647; Fax: 41-22-702-5702; E-mail:
Michel.Strubin@medecine.unige.ch.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Tan, E. Ehrlich, and X.-F. Yu DDB1 and Cul4A Are Required for Human Immunodeficiency Virus Type 1 Vpr-Induced G2 Arrest J. Virol., October 1, 2007; 81(19): 10822 - 10830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Mottet-Osman, F. Iseni, T. Pelet, M. Wiznerowicz, D. Garcin, and L. Roux Suppression of the Sendai Virus M Protein through a Novel Short Interfering RNA Approach Inhibits Viral Particle Production but Does Not Affect Viral RNA Synthesis J. Virol., March 15, 2007; 81(6): 2861 - 2868. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Schrofelbauer, Y. Hakata, and N. R. Landau HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1 PNAS, March 6, 2007; 104(10): 4130 - 4135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Han, L. Ding, B. Yuan, X. Yang, X. Wang, J. Li, Q. Lu, C. Huang, and Q. Ye Hepatitis B virus X protein and the estrogen receptor variant lacking exon 5 inhibit estrogen receptor signaling in hepatoma cells Nucleic Acids Res., June 6, 2006; 34(10): 3095 - 3106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Shimanouchi, K.-i. Takata, M. Yamaguchi, S. Murakami, G. Ishikawa, R. Takeuchi, Y. Kanai, T. Ruike, R. Nakamura, Y. Abe, et al. Drosophila Damaged DNA Binding Protein 1 Contributes to Genome Stability in Somatic Cells J. Biochem., January 1, 2006; 139(1): 51 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. C. Lee, J. Ren, E.-T. Wong, K. H. K. Ban, L. A. Lee, and C. G. L. Lee The Hepatitis B Virus X Protein Sensitizes HepG2 Cells to UV Light-induced DNA Damage J. Biol. Chem., September 30, 2005; 280(39): 33525 - 33535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Leupin, S. Bontron, C. Schaeffer, and M. Strubin Hepatitis B Virus X Protein Stimulates Viral Genome Replication via a DDB1-Dependent Pathway Distinct from That Leading to Cell Death J. Virol., April 1, 2005; 79(7): 4238 - 4245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-L. Sun and C. C.-K. Chao Cross-Resistance to Death Ligand-Induced Apoptosis in Cisplatin-Selected HeLa Cells Associated with Overexpression of DDB2 and Subsequent Induction of cFLIP Mol. Pharmacol., April 1, 2005; 67(4): 1307 - 1314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Bouchard and R. J. Schneider The Enigmatic X Gene of Hepatitis B Virus J. Virol., December 1, 2004; 78(23): 12725 - 12734. [Full Text] [PDF]
|
|
|
|
|
|
X. Liang, Y. C. Shin, R. E. Means, and J. U. Jung Inhibition of Interferon-Mediated Antiviral Activity by Murine Gammaherpesvirus 68 Latency-Associated M2 Protein J. Virol., November 15, 2004; 78(22): 12416 - 12427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. de Breyne, R. S. Monney, and J. Curran Proteolytic Processing and Translation Initiation: TWO INDEPENDENT MECHANISMS FOR THE EXPRESSION OF THE SENDAI VIRUS Y PROTEINS J. Biol. Chem., April 16, 2004; 279(16): 16571 - 16580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Leupin, S. Bontron, and M. Strubin Hepatitis B Virus X Protein and Simian Virus 5 V Protein Exhibit Similar UV-DDB1 Binding Properties To Mediate Distinct Activities J. Virol., June 1, 2003; 77(11): 6274 - 6283. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
