title: Group I p21-activated kinases facilitate Tax-mediated transcriptional activation of the human T-cell leukemia virus type 1 long terminal repeats.
abstract: BACKGROUND
  Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia and tropical spastic paraparesis. HTLV-1 encodes transactivator protein Tax that interacts with various cellular factors to modulate transcription and other biological functions. Additional cellular mediators of Tax-mediated transcriptional activation of HTLV-1 long terminal repeats (LTR) remain to be identified and characterized.
  
  
  RESULTS
  In this study, we investigated the regulatory role of group I p21-activated kinases (Paks) in Tax-induced LTR activation. Both wild-type and kinase-dead mutants of Pak3 were capable of potentiating the activity of Tax to activate LTR transcription. The effect of Paks on the LTR was attributed to the N-terminal regulatory domain and required the action of CREB, CREB-regulating transcriptional coactivators (CRTCs) and p300/CREB-binding protein. Paks physically associated with Tax and CRTCs. Paks were recruited to the LTR in the presence of Tax. siRNAs against either Pak1 or Pak3 prevented the interaction of Tax with CRTC1 and the recruitment of Tax to the LTR. These siRNAs also inhibited LTR-dependent transcription in HTLV-1-transformed MT4 cells and in cells transfected with an infectious clone of HTLV-1.
  
  
  CONCLUSIONS
  Group I Paks augment Tax-mediated transcriptional activation of HTLV-1 LTR in a kinase-independent manner.
authors.affiliation: Department of Biochemistry, The University of Hong Kong, 3/F Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong.
authors.forename: Ching-Ping
authors.initials: CP
authors.lastname: Chan
authors.forename: Yeung-Tung
authors.initials: YT
authors.lastname: Siu
authors.forename: Kin-Hang
authors.initials: KH
authors.lastname: Kok
authors.forename: Yick-Pang
authors.initials: YP
authors.lastname: Ching
authors.forename: Hei-Man Vincent
authors.initials: HM
authors.lastname: Tang
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Jin
mesh_terms: D016356:Gene Products, tax / Q000378:metabolism*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D011485:Protein Binding; D025941:Protein Interaction Mapping; D020079:Terminal Repeat Sequences; D015533:Transcriptional Activation; D014779:Virus Replication; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D016356:Gene Products, tax; C514970:tax protein, Human T-lymphotrophic virus 1; D054462:p21-Activated Kinases