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.

Abstract

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.

• Authors: Yumiko Nishinaka, Akira Nishiyama, Hiroshi Masutani, Shin-ichi Oka, Kaimul Md Ahsan, Yukie Nakayama, Yasuyuki Ishii, Hajime Nakamura, Michiyuki Maeda, Junji Yodoi
• Journal: Cancer research (Cancer Res) Vol. 64 Issue 4 Pg. 1287-92 (Feb 15 2004) ISSN: 0008-5472 [Print] United States
• PMID: 14983878 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Interleukin-2
• TXNIP protein, human
• Thioredoxins

Topics

• Carrier Proteins (analysis, genetics)
• Cell Cycle
• Cell Division
• Cell Line, Tumor
• Human T-lymphotropic virus 1 (isolation & purification)
• Humans
• Interleukin-2 (pharmacology)
• Leukemia-Lymphoma, Adult T-Cell (etiology)
• T-Lymphocytes (chemistry, virology)
• Thioredoxins