title: Cooperation of NF-kappaB2/p100 activation and the PDZ domain binding motif signal in human T-cell leukemia virus type 1 (HTLV-1) Tax1 but not HTLV-2 Tax2 is crucial for interleukin-2-independent growth transformation of a T-cell line.
abstract: Human T-cell leukemia virus type 1 (HTLV-1) but not HTLV-2 is associated with adult T-cell leukemia, and the distinct pathogenicity of these two closely related viruses is thought to stem from the distinct biological functions of the respective transforming proteins, HTLV-1 Tax1 and HTLV-2 Tax2. In this study, we demonstrate that Tax1 but not Tax2 interacts with NF-kappaB2/p100 and activates it by inducing the cleavage of p100 into the active transcription factor p52. Using RNA interference methods, we further show that NF-kappaB2/p100 is required for the transformation induced by Tax1, as determined by the ability to convert a T-cell line (CTLL-2) from interleukin-2 (IL-2)-dependent to -independent growth. While Tax2 shows a reduced transforming activity relative to Tax1, Tax2 fused with a PDZ domain binding motif (PBM) present only in Tax1 shows transforming activity equivalent to that of Tax1 in CTLL-2 cells expressing an inducer of p52 processing. These results reveal that the activation of NF-kappaB2/p100 plays a crucial role in the Tax1-mediated transformation of T cells and that NF-kappaB2/p100 activation and PBM function are both responsible for the augmented transforming activity of Tax1 relative to Tax2, thus suggesting that these Tax1-specific functions play crucial roles in HTLV-1 leukemogenesis.
authors: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan. mhiguchi@med.niigata-u.ac.jp
authors: Masaya
authors: M
authors: Higuchi
authors: Chikako
authors: C
authors: Tsubata
authors: Rie
authors: R
authors: Kondo
authors: Sakiko
authors: S
authors: Yoshida
authors: Masahiko
authors: M
authors: Takahashi
authors: Masayasu
authors: M
authors: Oie
authors: Yuetsu
authors: Y
authors: Tanaka
authors: Renaud
authors: R
authors: Mahieux
authors: Masao
authors: M
authors: Matsuoka
authors: Masahiro
authors: M
authors: Fujii
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D016356:Gene Products, tax / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D015367:Human T-lymphotropic virus 2 / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D007938:Leukemia / Q000473:pathology* / Q000821:virology; D051379:Mice; D052003:NF-kappa B p52 Subunit / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D016356:Gene Products, tax; D007376:Interleukin-2; D052003:NF-kappa B p52 Subunit; C498206:NFKB2 protein, human
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