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Journal of Virology, July 2002, p. 6495-6501, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6495-6501.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Turnover of Hepatitis B Virus X Protein Is Regulated by Damaged DNA-Binding Complex

Françoise Bergametti, Delphine Sitterlin,,{dagger} and Catherine Transy*

Unité de Recombinaison et Expression Génétique (INSERM U163), Institut Pasteur, Paris, France

Received 22 January 2002/ Accepted 25 March 2002

Mammalian hepatitis B viruses encode an essential regulatory protein, termed X, which may also be implicated in liver cancer development associated with chronic infection. X protein, also referred to as HBx in human virus and WHx in woodchuck virus, has been reported to bind to a number of cellular proteins, including the DDB1 subunit of the damaged DNA-binding (DDB) complex. Our previous work provided genetic evidence for the importance of WHx-DDB1 interaction in both the activity of the X protein and establishment of viral infection in woodchucks. In the present study, a direct action of DDB1 on the X protein is documented. Physical interaction between the two proteins leads to an increase in X protein stability. This effect results from protection of the viral protein from proteasome-mediated degradation. Protection of WHx is overcome in the presence DDB2, the second subunit of the DDB heterodimer. In keeping with observations reported for HBx, DDB2 was found to directly bind to WHx. Nonetheless, the counteracting effect of DDB2 on X stabilization requires DDB2-DDB1 interaction. Taken together, these findings substantiate the physical and functional connection between the X protein and the DDB1-DDB2 heterodimer, leading to the regulation of the pool of the viral protein.


* Corresponding author. Mailing address: UREG/INSERM U163, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone: (33) 1 45 68 88 51. Fax: (33) 1 45 68 89 43. E-mail: ctransy{at}pasteur.fr.

{dagger} Present address: Laboratoire de Génétique et de Biologie Cellulaire (UPRESA 8087), Université de Versailles, Versailles, France.


Journal of Virology, July 2002, p. 6495-6501, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6495-6501.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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