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Cited by 593

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

HTLV-I basic leucine zipper factor gene mRNA supports proliferation of adult T cell leukemia cells

Open access
Satou, Yorifumi, Yasunaga, Jun-ichirou, Yoshida, Mika, Matsuoka, Masao·2006·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0507631103
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Abstract

Human T cell leukemia virus type I (HTLV-I) causes adult T cell leukemia (ATL) in 2–5% of carriers after a long latent period. An HTLV-I encoded protein, Tax, induces proliferation and inhibits apoptosis, resulting in clonal proliferation of infected cells. However, tax gene expression in ATL cells is disrupted by several mechanisms, including genetic changes in the tax gene and DNA methylation/deletion of the 5′ long terminal repeat (LTR). Because Tax is the major target of cytotoxic T-lymphocytes in vivo , loss of Tax expression should enable ATL cells to escape the host immune system. The 5′ LTR of HTLV-I is frequently hypermethylated or deleted in ATL cells, whereas the 3′ LTR remains unmethylated and intact, suggesting the involvement of the 3′ LTR in leukemogenesis. Here we show that a gene encoded by the minus strand of the HTLV-I proviral genome, HTLV-I basic leucine zipper factor ( HBZ ), is transcribed from 3′-LTR in all ATL cells. Suppression of HBZ gene transcription by short interfering RNA inhibits proliferation of ATL cells. In addition, HBZ gene expression promotes proliferation of a human T cell line. Analyses of T cell lines transfected with mutated HBZ genes showed that HBZ promotes T cell proliferation in its RNA form, whereas HBZ protein suppresses Tax-mediated viral transcription through the 5′ LTR. Thus, the single HBZ gene has bimodal functions in two different molecular forms. The growth-promoting activity of HBZ RNA likely plays an important role in oncogenesis by HTLV-I.

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Metadata

Authors
Satou, Y., Yasunaga, J.-I., Yoshida, M., & Matsuoka, M.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
2006-01-09
Volume
103
Issue
3
Pages
720-725
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0507631103
OpenAlex
W2071794490
Cited by
593
References
4
FWCI
9.26
Type
journal article
Language
en
Open access
green

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