Human T cell leukemia virus type I tax-induced I?B-? modulates tax-dependent and tax-independent gene expression in T cells.

ABSTRACT: Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia (ATL) and various inflammatory disorders including HTLV-I-associated myelopathy/tropical spastic paraparesis. HTLV-I oncoprotein Tax is known to cause permanent activation of many cellular transcription factors including nuclear factor-?B (NF-?B), cyclic adenosine 3',5'-monophosphate response element-binding protein, and activator protein 1 (AP-1). Here, we show that NF-?B-binding cofactor inhibitor of NF-?B-? (I?B-?) is constitutively expressed in HTLV-I-infected T cell lines and ATL cells, and Tax transactivates the I?B-? gene, mainly through NF-?B. Microarray analysis of I?B-?-expressing uninfected T cells demonstrated that I?B-? induced the expression of NF-?B. and interferon-regulatory genes such as B cell CLL/lymphoma 3 (Bcl3), guanylate-binding protein 1, and signal transducer and activator of transcription 1. The transcriptional activation domain, nuclear localization signal, and NF-?B-binding domain of I?B-? were required for Bcl3 induction, and I?B-? synergistically enhanced Tax-induced Bcl3 transactivation in an NF-?B-dependent manner. Interestingly, I?B-? inhibited Tax-induced NF-?B, AP-1 activation, and HTLV-I transcription. Furthermore, I?B-? interacted with Tax in vitro and this interaction was also observed in an HTLV-I-transformed T cell line. These results suggest that I?B-? modulates Tax-dependent and Tax-independent gene transcription in T cells. The function of I?B-? may be of significance in ATL genesis and pathogenesis of HTLV-I-associated diseases.

SUBMITTER: Kimura R 

PROVIDER: S-EPMC3769889 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature