oxidants and antioxidants in biology - Oxygen Club of California

Thioredoxin Binding Protein TBP-2/VDUP1:
Involvement in Cell Cycle and Aging
YUMIKO NISHINAKA 1 , AHSAN MD. KAIMUL 2 ,
HIROSHI MASUTANI 1, 2 , TOHRU YOSHIDA 2 , MICHIYUKI MAEDA 3 ,
AND
JUNJI YODOI 1,2
1 Human Stress Signal Research Center, National Institute of Advanced Industrial
Science and Technology (AIST), Midorigaoka, Ikeda, Osaka 563-8577,
Japan; 2 Department of Biological Responses, Institute for Virus Research, Kyoto
University, 5; 3 Shogoin, Kawahara-cho, Sakyo, Kyoto 606-8507, Japan;
3Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin,
Kawahara-cho, Sakyo, Kyoto 606-8507, Japan
Thioredoxin (TRX) is one of the vital components of the thiol
reducing system and plays multiple roles in cellular processes such
as gene expression, cell proliferation and apoptosis. TRX expression
is induced by a variety of oxidative stimuli, including UV irradiation,
inflammatory cytokines or chemical carcinogens. We have
identified TRX binding protein-2 (TBP-2), identical to vitamin D3
up-regulated protein 1 (VDUP1) as a negative regulator of TRX on
its expression and reducing activity (1).
Expression of TBP-2 is lost in HTLV-I-positive IL-2-
independent T-cell lines, but maintained in HTLV-I-positive IL-2-
dependent T-cell lines as well as HTLV-I-negative T-cell lines.
Ectopic overexpression of TBP-2 in HTLV-I-positive T-cells resulted
in growth suppression accompanied by a decrease of TRX
reducing activity. In the TBP-2-overexpressing cells, G1 arrest was
observed in association with an increase of p16 expression and reduction
of Rb phosphorylation. The results suggest that TBP-2
plays a crucial role in the growth regulation of T-cells through the
interaction with its target molecules including TRX. Therefore, loss
of TBP-2 expression may be involved in the multistep oncogenic
process of HTLV-I transformation. The modulation of TRX functions
may be a new therapeutic strategy for the treatment of HTLV-
I related diseases (2).
We have shown that TRX overexpressed mice show a significant
resistancy against variety of oxidative stresses, showing increased
longevity (3). As TBP-2 is a negative regulator of TRX, we
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