HTLV-1 basic leucine zipper factor downregulates cyclin D1 expression via interactions with NF-κB.

Abstract:

:Human T cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus. It can cause adult T cell leukemia (ATL) and other diseases. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ), which is encoded by the minus-strand of the provirus, is expressed in all cases of ATL and involved in T cell proliferation. However, the exact mechanism underlying its growth-promoting activity is poorly understood. Herein, we demonstrated that HBZ suppressed cyclin D1 expression by inhibiting the nuclear factor (NF)-κB signaling pathway. Among the potential mechanisms of cyclin D1 inhibition mediated by HBZ, we found that HBZ suppressed cyclin D1 promoter activity. Luciferase assay analysis revealed that HBZ repressed cyclin D1 promoter activity by suppressing NF-κB‑driven transcription mediated by the p65 subunit. Using an immunoprecipitation assay, we found that HBZ could bind to p65, but not p50. Finally, we showed that HBZ selectively interacted with p65 via its AD+bZIP domains. By suppressing cyclin D1 expression, HBZ can alter cell cycle progression of HTLV-1-infected cells, which may be critical for oncogenesis.

journal_name

Int J Mol Med

authors

Ma Y,Zhang B,Wang D,Qian L,Song X,Wang X,Yang C,Zhao G

doi

10.3892/ijmm.2017.2868

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

764-770

issue

3

eissn

1107-3756

issn

1791-244X

journal_volume

39

pub_type

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