PDZ domain-binding motif of human T-cell leukemia virus type 1 Tax oncoprotein is essential for the interleukin 2 independent growth induction of a T-cell line.
BACKGROUND
Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL), whereas HTLV type 2 (HTLV-2), is not associated with ATL or any other leukemia. HTLV-1 encodes the transforming gene tax1, whose expression in an interleukin (IL)-2-dependent T-cell line (CTLL-2) induces IL-2-independent growth.


RESULTS
In this study, we demonstrated that IL-2-independent growth induction by Tax1 was abrogated by mutations of the PDZ domain-binding motif (PBM) at the Tax1 C-terminus. HTLV-2 Tax2, which shares 75% amino acid identity with Tax1 but does not have a PBM, was not able to induce IL-2-independent growth of CTLL-2.


CONCLUSIONS
Our results suggest that Tax1, through interaction with PDZ domain protein(s) induces IL-2-independent growth, which may be a factor in multi-step leukemogenesis caused by HTLV-1.
Tsubata
Chikako
C
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan. chikakot@med.niigata-u.ac.jp
Higuchi
Masaya
M
Takahashi
Masahiko
M
Oie
Masayasu
M
Tanaka
Yuetsu
Y
Gejyo
Fumitake
F
Fujii
Masahiro
M
D001665:Binding Sites; D002460:Cell Line; D049109:Cell Proliferation; D016356:Gene Products, tax / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000209:etiology; D016328:NF-kappa B / Q000502:physiology
D016356:Gene Products, tax; D007376:Interleukin-2; D016328:NF-kappa B