Hepatitis B virus pX activates NF-κB-dependent transcription through a raf-independent pathway

Paolo Chirillo, Mirella Falco, Pier Lorenzo Puri, Marco Artini, Clara Balsano, Massimo Levrero, Gioacchino Natoli

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

In this study, we characterized the molecular events involved in the activation of the ubiquitous transcription factor NF-κB by the viral transactivator pX. pX expression in HeLa cells determines a manyfold increase in NF-κB-dependent transcription, which is associated with an increase in p50/p65 heterodimer DNA-binding activity. Since the IκB-α inhibitory subunit proteolytic degradation, which follows its phosphorylation/modification, is a key event in NF-κB activation by different stimuli (such as growth factors, phorbol esters, tumor necrosis factor, UV irradiation, and oxygen radicals), we investigated pX effects on IκB-α, as well as the possible involvement of known signalling pathways in pX-induced NF-κB-dependent transcription. We observed that although pX had no direct effect on p50 or p65, it was able to restore the IκB-α-suppressed p50/p65 activity. More directly, the stable expression of pX in HeLa cells resulted in reduced levels of IκB-α in the cytoplasm. Pretreatment of the cells with H7, calphostin C, tyrphostin 25, or N-acetylcysteine did not impair the effects of pX on NF-κB, thus ruling out the involvement of protein kinase C, tyrosine kinases, and oxygen radicals. Finally, while most of the known NF-κB-activating agents converge on Raf-1 protein kinase, when Raf-1 activity is blocked by overexpression of a dominant negative mutant, the effects of pX on NF-κB are not impaired. Thus, we suggest that although pX is able to activate the Ras/Raf-1-signalling pathway, it triggers NF-κB activation by an as yet unidentified Raf-1-independent pathway.

Original languageEnglish
Pages (from-to)641-646
Number of pages6
JournalJournal of Virology
Volume70
Issue number1
Publication statusPublished - 1996

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Proto-Oncogene Proteins c-raf
Hepatitis B virus
HeLa Cells
Reactive Oxygen Species
transcription (genetics)
Trans-Activators
reactive oxygen species
Acetylcysteine
Phorbol Esters
Protein-Tyrosine Kinases
Protein Kinases
Intercellular Signaling Peptides and Proteins
acetylcysteine
Cytoplasm
Transcription Factors
Tumor Necrosis Factor-alpha
tumor necrosis factors
Phosphorylation
protein kinase C
cells

ASJC Scopus subject areas

  • Immunology

Cite this

Hepatitis B virus pX activates NF-κB-dependent transcription through a raf-independent pathway. / Chirillo, Paolo; Falco, Mirella; Puri, Pier Lorenzo; Artini, Marco; Balsano, Clara; Levrero, Massimo; Natoli, Gioacchino.

In: Journal of Virology, Vol. 70, No. 1, 1996, p. 641-646.

Research output: Contribution to journalArticle

Chirillo, P, Falco, M, Puri, PL, Artini, M, Balsano, C, Levrero, M & Natoli, G 1996, 'Hepatitis B virus pX activates NF-κB-dependent transcription through a raf-independent pathway', Journal of Virology, vol. 70, no. 1, pp. 641-646.
Chirillo P, Falco M, Puri PL, Artini M, Balsano C, Levrero M et al. Hepatitis B virus pX activates NF-κB-dependent transcription through a raf-independent pathway. Journal of Virology. 1996;70(1):641-646.
Chirillo, Paolo ; Falco, Mirella ; Puri, Pier Lorenzo ; Artini, Marco ; Balsano, Clara ; Levrero, Massimo ; Natoli, Gioacchino. / Hepatitis B virus pX activates NF-κB-dependent transcription through a raf-independent pathway. In: Journal of Virology. 1996 ; Vol. 70, No. 1. pp. 641-646.
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AU - Chirillo, Paolo

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