Hepatitis C virus core protein regulates p300/CBP co-activation function. Possible role in the regulation of NF-AT1 transcriptional activity.
Hepatitis C virus (HCV) core is a viral structural protein; it also participates in some cellular processes, including transcriptional regulation. However, the mechanisms of core-mediated transcriptional regulation remain poorly understood. Oncogenic virus proteins often target p300/CBP, a known co-activator of a wide variety of transcription factors, to regulate the expression of cellular and viral genes. Here we demonstrate, for the first time, that HCV core protein interacts with p300/CBP and enhances both its acetyl-transferase and transcriptional activities. In addition, we demonstrate that nuclear core protein activates the NH2-terminal transcription activation domain (TAD) of NF-AT1 in a p300/CBP-dependent manner. We propose a model in which core protein regulates the co-activation function of p300/CBP and activates NF-AT1, and probably other p300/CBP-regulated transcription factors, by a novel mechanism involving the regulation of the acetylation state of histones and/or components of the transcriptional machinery.
Gómez-Gonzalo
Marta
M
Unidad de Biología Molecular, Hospital Universitario de la Princesa, 28006 Madrid, Spain.
Benedicto
Ignacio
I
Carretero
Marta
M
Lara-Pezzi
Enrique
E
Maldonado-Rodríguez
Alejandra
A
Moreno-Otero
Ricardo
R
Lai
Michael M C
MM
López-Cabrera
Manuel
M
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D016174:Hepacivirus / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D050811:Octamer Transcription Factor-1; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D014758:Viral Core Proteins; D000123:Acetyltransferases; D002118:Calcium