NDLI: HTLV-1 Proviruses Encoding Non-Functional TAX in Adult T-Cell Leukemia

Content Provider	Springer Nature Link
Author	Okazaki, Satoru Moriuchi, Ryozo Yosizuka, Naoto Sugahara, Kazuyuki Maeda, Takahiro Jinnai, Itsuro Tomonaga, Masao Kamihira, Shimeru Katamine, Shigeru
Copyright Year	2001
Abstract	Adult T-cell leukemia (ATL) is associated with prior infection with human T-cell leukemia virus type 1 (HTLV-1). TAX, the major transactivator of HTLV-1, has been implicated in the immortalization of infected T-cells, but molecular mechanisms of in vivo malignant cell transformation induced by HTLV-1 remain unclear. To investigate the role of TAX in the monoclonal proliferation of ATL cells, we determined the nucleotide sequence of tax DNA clones obtained from 6 ATL patients and analysed the biological function of their products. We found that ATL cells from 2 of these patients possessed tax with a nonsense or frame-shift mutation resulting in the premature termination of its protein product, which was no longer functional. This strongly argued against an indispensable role of TAX for the maintenance of ATL cells in vivo. On the other hand, the frequency of nucleotide substitutions found in non-functional tax DNA clones from these patients was significantly lower than those in functional tax DNA clones from the others, suggesting a role for TAX in the genome instability of infected cells. Although mismatch repair defects in the microsatellite markers, including those in hMSH3, hMSH6, BAX, TGF-β RII, and E2F4 genes, were infrequent, we found an increase in the number of CAG repeats of the E2F4 microsatellite marker in 1 patient. These findings indicate that while TAX may be a necessary prerequisite for malignant transformation of infected cells, it is not essential for the maintenance of ATL cells in vivo.
Starting Page	123
Ending Page	135
Page Count	13
File Format	PDF
ISSN	09208569
Journal	Virus Genes
Volume Number	23
Issue Number	2
e-ISSN	1572994X
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	2001-01-01
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Medical Microbiology Virology Plant Sciences
Content Type	Text
Resource Type	Article
Subject	Virology Genetics Medicine Molecular Biology

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The PDZ domain binding motif (PBM) of human T-cell leukemia virus type 1 Tax can be substituted by heterologous PBMs from viral oncoproteins during T-cell transformation

Human T cell leukemia virus type 2 (HTLV-2) Tax2 has a dominant activity over HTLV-1 Tax1 to immortalize human CD4$^{+}$ T cells

Human T-cell Leukemia Virus Type-I (HTLV-I) Tax is not the Only One Factor to Enhance Human Immunodeficiency Virus Type-1 (HIV-1) Infection in Culture-supernatants

Tax & Rex: Overlapping Genes of the Deltaretrovirus Group

Human T-cell leukemia virus type 1 (HTLV-1) Tax1 oncoprotein but not HTLV-2 Tax2 induces the expression of OX40 ligand by interacting with p52/p100 and RelB

The pleiotropic protein kinase CK2 phosphorylates HTLV-1 Tax protein in vitro, targeting its PDZ-binding motif

Human T-cell leukemia virus type 1 Tax induces an aberrant clustering of the tumor suppressor Scribble through the PDZ domain-binding motif dependent and independent interaction

Development of T cell lymphoma in HTLV-1 bZIP factor and Tax double transgenic mice

Knockdown of synapse-associated protein Dlg1 reduces syncytium formation induced by human T-cell leukemia virus type 1

HTLV-1 Proviruses Encoding Non-Functional TAX in Adult T-Cell Leukemia

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The PDZ domain binding motif (PBM) of human T-cell leukemia virus type 1 Tax can be substituted by heterologous PBMs from viral oncoproteins during T-cell transformation

Human T cell leukemia virus type 2 (HTLV-2) Tax2 has a dominant activity over HTLV-1 Tax1 to immortalize human CD4$^{+}$ T cells

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