Loss of thioredoxin-binding protein-2/vitamin D3 up-regulated protein 1 in human T-cell leukemia virus type I-dependent T-cell transformation: implications for adult T-cell leukemia leukemogenesis.
Human T-cell leukemia virus type I (HTLV-I) is the causative agent of adult T-cell leukemia (ATL). However, the low incidence of ATL among HTLV-I-infected carriers, together with a long latent period, suggests that multiple host-viral events are involved in the progression of HTLV-I-dependent transformation and subsequent development of ATL. Human thioredoxin (TRX) is a redox active protein highly expressed in HTLV-I-transformed cell lines, whereas the TRX-binding protein-2/vitamin D3 up-regulated protein 1 (TBP-2/VDUP1) was recently identified as a negative regulator of TRX. We report here that expression of TBP-2 is lost in HTLV-I-positive, interleukin-2-independent T-cell lines but maintained in HTLV-I-positive, interleukin-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. In the TBP-2-overexpressing cells, a G1 arrest was observed in association with an increase of p16 expression and reduction of retinoblastoma phosphorylation. The results suggest that TBP-2 plays a crucial role in the growth regulation of T cells and that the loss of TBP-2 expression in HTLV-I-infected T cells is one of the key events involved in the multistep progression of ATL leukemogenesis.
Biomedical Special Research Unit, Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Midorigaoka, Ikeda, Osaka, Japan.
Yumiko
Y
Nishinaka
Akira
A
Nishiyama
Hiroshi
H
Masutani
Shin-ichi
S
Oka
Kaimul Md
KM
Ahsan
Yukie
Y
Nakayama
Yasuyuki
Y
Ishii
Hajime
H
Nakamura
Michiyuki
M
Maeda
Junji
J
Yodoi
D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000209:etiology*; D013601:T-Lymphocytes / Q000737:chemistry* / Q000821:virology*; D013879:Thioredoxins
D002352:Carrier Proteins; D007376:Interleukin-2; C486715:TXNIP protein, human; D013879:Thioredoxins