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.
Nishinaka
Yumiko
Y
Biomedical Special Research Unit, Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Midorigaoka, Ikeda, Osaka, Japan.
Nishiyama
Akira
A
Masutani
Hiroshi
H
Oka
Shin-ichi
S
Ahsan
Kaimul Md
KM
Nakayama
Yukie
Y
Ishii
Yasuyuki
Y
Nakamura
Hajime
H
Maeda
Michiyuki
M
Yodoi
Junji
J
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