title: Interplay between the HTLV-2 Tax and APH-2 proteins in the regulation of the AP-1 pathway.
abstract: BACKGROUND
  In contrast with human T-cell leukemia virus type 1 (HTLV-1) that causes ATL (adult T-cell leukemia), HTLV-2 has not been causally linked to malignant disease. The minus strand of the HTLV genomes encode the regulatory proteins HTLV-1 bZIP factor (HBZ) for HTLV-1 and antisense protein of HTLV-2 (APH-2) for HTLV-2. Unlike the viral proteins Tax1 and Tax2, both HBZ and APH-2 are constitutively expressed in infected cells suggesting that they may play important roles in the pathogenesis of these viruses. To date, very little is known about the function of APH-2 except that it inhibits Tax2-mediated transcription of HTLV-2 genes. In the present study, we investigated the role of APH-2 in basal and Tax2B-mediated activation of the AP-1 pathway.
  
  
  RESULTS
  We demonstrate that, unlike HBZ, APH-2 stimulates basal AP-1 transcription by interacting with c-Jun and JunB through its non-conventional bZIP domain. In addition, when Tax2 and APH-2 are co-expressed, they physically interact in vivo and in vitro and APH-2 acts as an inhibitor of Tax2-mediated activation of AP-1 transcription.
  
  
  CONCLUSIONS
  This report is the first to document that HTLV-2 can modulate the AP-1 pathway. Altogether our results reveal that, in contrast with HBZ, APH-2 regulates AP-1 activity in a Tax2-dependant manner. As the AP-1 pathway is involved in numerous cellular functions susceptible to affect the life cycle of the virus, these distinct biological properties between HBZ and APH-2 may contribute to the differential pathogenic potential of HTLV-1 and HTLV-2.
authors.affiliation: Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland. cmarban@unistra.fr
authors.forename: Céline
authors.initials: C
authors.lastname: Marban
authors.forename: Aine
authors.initials: A
authors.lastname: McCabe
authors.forename: Terence N
authors.initials: TN
authors.lastname: Bukong
authors.forename: William W
authors.initials: WW
authors.lastname: Hall
authors.forename: Noreen
authors.initials: N
authors.lastname: Sheehy
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D017364:Collagenases / Q000235:genetics; D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000378:metabolism*; D015367:Human T-lymphotropic virus 2 / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D016356:Gene Products, tax; D008562:Membrane Glycoproteins; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; C413604:nicastrin protein; C514971:tax protein, Human T-lymphotrophic virus 2; D053829:Amyloid Precursor Protein Secretases; D017364:Collagenases