UVDDB p127-binding modulates activities and intracellular distribution of hepatitis B virus X protein

被引:44
作者
Sitterlin, D [1 ]
Bergametti, F [1 ]
Transy, C [1 ]
机构
[1] Inst Pasteur, Unite Recombinais & Express Genet, INSERM, U163, F-75724 Paris 15, France
关键词
hepatitis B virus; X protein; UV-damaged DNA-binding protein; transactivation; apoptosis; nuclear import;
D O I
10.1038/sj.onc.1203771
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mammalian hepatitis B, viruses encode a unique regulatory protein termed X, which is essential for infection and likely plays a role in the carcinogenic process associated with hepadnaviral infection. Among the numerous properties ascribed to X protein, two have been widely documented: promiscuous transcriptional transactivation and proapoptosis. However, full understanding of the mechanisms underlying these activities requires the identification of the genuine X partners among the multiple X-binding: host proteins. Here we show that (i) mutations in X protein, which markedly alter affinity for the host protein UVDDBp127, inactivate both transactivation and proapoptosis; (ii) ectopic fusion of a functional UVDDB-binding domain to a deficient binding;X mutant restored its activity; (iii) in contrast to the loss-of-binding mutants, a mutant with a strong gain-of-binding exerted trans-dominant negative effects on wt X activity and localized in the nucleus and (iv) increase in intracellular UVDDB concentration enhanced both wt X-mediated transactivation and apoptosis, Taken together, our data provide strong evidence for a common upstream step in X mode of action, consisting of its productive interaction with UVDDB, via a structurally and functionally autonomous module. In addition, they underscore a nuclear location step of the viral protein that depends on its ability to bind UVDDB.
引用
收藏
页码:4417 / 4426
页数:10
相关论文
共 41 条
  • [1] BEASLEY RP, 1981, LANCET, V2, P1129
  • [2] Hepatitis B virus X protein interferes with cellular DNA repair
    Becker, SA
    Lee, TH
    Butel, JS
    Slagle, BL
    [J]. JOURNAL OF VIROLOGY, 1998, 72 (01) : 266 - 272
  • [3] Hepatitis B virus HBx protein induces transcription factor AP-1 by activation of extracellular signal-regulated and c-Jun N-terminal mitogen-activated protein kinases
    Benn, J
    Su, F
    Doria, M
    Schneider, RJ
    [J]. JOURNAL OF VIROLOGY, 1996, 70 (08) : 4978 - 4985
  • [4] Benning H, 1995, Ger J Ophthalmol, V4, P11
  • [5] The proapoptotic effect of hepatitis B virus HBx protein correlates with its transactivation activity in stably transfected cell lines
    Bergametti, F
    Prigent, S
    Luber, B
    Benoit, A
    Tiollais, P
    Sarasin, A
    Transy, C
    [J]. ONCOGENE, 1999, 18 (18) : 2860 - 2871
  • [6] Cadwell R C, 1992, PCR Methods Appl, V2, P28, DOI 10.1101/gr.2.1.28
  • [7] HUMAN RPB5, A SUBUNIT SHARED BY EUKARYOTIC NUCLEAR-RNA POLYMERASES, BINDS HUMAN HEPATITIS-B VIRUS X-PROTEIN AND MAY PLAY A ROLE IN X-TRANSACTIVATION
    CHEONG, JH
    YI, MK
    LIN, Y
    MURAKAMI, S
    [J]. EMBO JOURNAL, 1995, 14 (01) : 143 - 150
  • [8] The hepatitis B virus X gene induces p53-mediated programmed cell death
    Chirillo, P
    Pagano, S
    Natoli, G
    Puri, PL
    Burgio, VL
    Balsano, C
    Levrero, M
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (15) : 8162 - 8167
  • [9] Hepatitis B virus pX activates NF-kappa B-dependent transcription through a Raf-independent pathway
    Chirillo, P
    Falco, M
    Puri, PL
    Artini, M
    Balsano, C
    Levrero, M
    Natoli, G
    [J]. JOURNAL OF VIROLOGY, 1996, 70 (01) : 641 - 646
  • [10] TRANSCRIPTIONAL ACTIVATION OF HOMOLOGOUS AND HETEROLOGOUS GENES BY THE HEPATITIS-B VIRUS X-GENE PRODUCT IN CELLS PERMISSIVE FOR VIRAL REPLICATION
    COLGROVE, R
    SIMON, G
    GANEM, D
    [J]. JOURNAL OF VIROLOGY, 1989, 63 (09) : 4019 - 4026