The hepatitis B virus X protein binds to and activates the NH(2)-terminal trans-activation domain of nuclear factor of activated T cells-1.
We have previously reported that the hepatitis B virus X protein (HBx) activates nuclear factor of activated T cells (NF-AT), a key regulator of the immune system, by a calcium/calcineurin-dependent pathway, involving dephosphorylation and nuclear translocation of this transcription factor. In addition, we showed that HBx synergizes with potent calcium-mobilizing stimuli to activate NF-AT-dependent transcription, suggesting that additional mechanisms might also be operative in the activation of NF-AT by HBx. Here we demonstrate that HBx activates the NH(2)-terminal transcription activation domain (TAD) of NF-AT1 by a mechanism involving protein-protein interaction. Targeting of HBx to the nucleus did not affect its ability to induce the transcriptional activity of NF-AT1. In contrast, mutations of HBx affecting its functional interaction with general transcription factors abrogated the HBx-induced activity of NF-AT1. Together these results indicate that HBx may exert its function by acting as a nuclear coactivator of NF-AT1.
Carretero
Marta
M
Unidad de Biología Molecular, Hospital Universitario de la Princesa, C/Diego de León 62, 28006 Madrid, Spain.
Gómez-Gonzalo
Marta
M
Lara-Pezzi
Enrique
E
Benedicto
Ignacio
I
Aramburu
José
J
Martínez-Martínez
Sara
S
Redondo
Juan Miguel
JM
López-Cabrera
Manuel
M
D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation; D054334:Viral Regulatory and Accessory Proteins
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein