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Human T-cell leukemia virus type 1 Tax transactivates the matrix metalloproteinase 7 gene via JunD/AP-1 signaling

Lookup NU author(s): Professor Derek Mann


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Adult T-cell leukemia (ATL) is a T-cell malignancy associated with human T-cell leukemia virus type 1 (HTLV-1) and characterized by visceral invasion. Degradation of the extracellular matrix by matrix metalloproteinases (MMPs) is a crucial process in invasion of tumors and metastasis. MMP-7 (or matrilysin), is a "minimal domain MMP" with proteolytic activity against components of the extracellular matrix. To determine the involvement of MMP-7 in visceral spread in An, this study investigated MMP-7 expression in ATL MMP-7 expression was identified in HTLV-1-infected T-cell lines, peripheral blood ATL cells and ATL cells in lymph nodes, but not in uninfected T-cell lines or normal peripheral blood mononuclear cells. MMP-7 expression was induced following infection of a human T-cell line with HTLV-1, and specifically by the viral protein Tax. Functionally, MMP-7 promoted cell migration of HTLV-1-infected T cells. The MMP-7 promoter activity was increased by Tax and reduced by deletion of the activator protein-1 (AP-1) binding site. Electrophoretic mobility shift assay showed high levels of AP-1 binding proteins, including JunD, in HTLV-1-infected T-cell lines and An cells, and Tax elicited JunD binding to the MMP-7 AP-1 element. Tax-induced MMP-7 activation was inhibited by dominant negative JunD and augmented by JunD/JunD homodimers. Short interfering RNA against JunD inhibited MMP-7 mRNA expression in HTLV-1-infected T-cell lines. These results suggest that the induction of MMP-7 by Tax is regulated by JunD and that MMP-7 could facilitate visceral invasion in ATL. (C) 2011 Elsevier B.V. All rights reserved.

Publication metadata

Author(s): Nakachi S, Nakazato T, Ishikawa C, Kimura I, Mann DA, Senba M, Masuzaki H, Mori N

Publication type: Article

Publication status: Published

Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Year: 2011

Volume: 1813

Issue: 5

Pages: 731-741

Print publication date: 10/02/2011

ISSN (print): 0167-4889

ISSN (electronic):

Publisher: Elsevier BV


DOI: 10.1016/j.bbamcr.2011.02.002


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