HTLV-I Tax trans-activation and cell growth signaling.
We have cloned two genes for cell surface molecules, capable of delivering the intracellular signals, which are modulated for their expression by Tax. One is the gamma chain of the interleukin-2 (IL-2) receptor which is suggested to be critical for IL-2-dependent growth of human T-cell leukemia virus type I (HTLV-I) infected cells. The gamma chain is upregulated by Tax, like the IL-2 receptor alpha chain. This upregulation may compensate the gamma chain downregulation after IL-2 binding, presumably resulting in more frequent growth of HTLV-I infected T cells. The other is gp34 that was initially identified as a molecule specifically expressed on HTLV-I-infected T cells. gp34 has been demonstrated to bind OX40 which belongs to the tumor necrosis factor (TNF) receptor family. We found that HTLV-I Tax induces expression of gp34 and OX40, and that normal T cell transiently express both gp34 and OX40 upon antigenic stimulation. Collectively, it may be possible that HTLV-I-infected T cells are in a predisposition to growth due to modulated expression by HTLV-I Tax of gp34/OX40 and the gamma chain.
Nakamura
M
M
Human Gene Sciences Center, Tokyo Medical and Dental University, Japan.
Takasawa
N
N
Ohbo
K
K
Higashimura
N
N
Ohtani
K
K
Tanaka
Y
Y
Sugamura
K
K
D002455:Cell Division; D002460:Cell Line; D003001:Cloning, Molecular; D015536:Down-Regulation; D016356:Gene Products, tax / Q000096:biosynthesis / Q000378:metabolism*; D017930:Genes, Reporter; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000502:physiology*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D014158:Transcription, Genetic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D015854:Up-Regulation
D016356:Gene Products, tax; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C505716:TNFRSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D008156:Luciferases