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Journal of Virology, October 1999, p. 7981-7987, Vol. 73, No. 10
Department of
Immunotherapeutics1 and Department of
Molecular Virology,
Received 10 February 1999/Accepted 14 June 1999
Human T-cell leukemia virus type 1 (HTLV-1) Tax is thought to play
a pivotal role in immortalization of T cells. We have recently shown
that the expression of Tax protected the mouse T-cell line CTLL-2
against apoptosis induced by interleukin-2 (IL-2) deprivation and
converted its growth from being IL-2 dependent to being IL-2 independent. In this study, we demonstrate that constitutive expression of bcl-xl but not bcl-2, bcl-xs,
bak, bad, or bax was associated with apoptosis resistance after IL-2 deprivation in CTLL-2 cells that
expressed Tax. Transient-transfection assays showed that bcl-x promoter was transactivated by wild-type Tax. Similar
effects were observed in mutant Tax retaining transactivating ability through NF-
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Induction of Bcl-xL Expression by Human T-Cell
Leukemia Virus Type 1 Tax through NF-
B in
Apoptosis-Resistant T-Cell Transfectants with Tax
B. Deletion or substitution of a putative NF-
B binding site identified in the bcl-x promoter significantly
decreased Tax-induced transactivation. This NF-
B-like element was
able to form a complex with NF-
B family proteins in vitro.
Furthermore, Tax-induced transactivation of the bcl-x
promoter was also diminished by the mutant I
B
, which specifically
inhibits NF-
B activity. Our findings suggest that constitutive
expression of Bcl-xL induced by Tax through the NF-
B
pathway contributes to the inhibition of apoptosis in CTLL-2 cells
after IL-2 deprivation.
*
Corresponding author. Mailing address: Department of
Immunotherapeutics, Tokyo Medical and Dental University, Medical
Research Division, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113, Japan. Phone: 81 (3) 5803-5798. Fax: 81 (3) 5803-0235. E-mail:
kann.impt{at}med.tmd.ac.jp.
Journal of Virology, October 1999, p. 7981-7987, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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