Bcl-3, induced by Tax and HTLV-1, inhibits NF-κB activation and promotes autophagy

• Published in: Cellular signalling 2013-12, Vol.25 (12), p.2797-2804
• Main Authors: Wang, Jinheng, Niu, Zhiguo, Shi, Ying, Gao, Cai, Wang, Xia, Han, Jingxian, Li, Junying, Gao, Zhitao, Zhu, Xiaofei, Song, Xiangfeng, Qin, Zhihai, Wang, Hui
• Format: Article
• Language: English
• Subjects: Autophagy; Bcl-3; Gene Expression Regulation, Neoplastic; Gene Products, tax - immunology; HeLa Cells; HTLV-1; HTLV-I Infections - genetics; HTLV-I Infections - immunology; HTLV-I Infections - virology; Human T-lymphotropic virus 1; Human T-lymphotropic virus 1 - immunology; Humans; Jurkat Cells; Lymphoma, T-Cell - genetics; Lymphoma, T-Cell - immunology; Lymphoma, T-Cell - virology; NF-kappa B - immunology; NF-κB activation; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - immunology; Signal Transduction; T-Lymphocytes - immunology; T-Lymphocytes - virology; Tax; Transcription Factors - genetics; Transcription Factors - immunology; Transcriptional Activation
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2013.09.010

The human T cell leukemia virus type 1 (HTLV-1) is a complex human retrovirus that causes an aggressive leukemia known as adult T cell leukemia (ATL). The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway, which is perceived as the primary cause of ATL. Bcl-3, a member of the NF-κB inhibitor (IκB) family, is highly expressed in many HTLV-1-infected T cell lines and ATL cells. However, the role of Bcl-3 in Tax-induced NF-κB activation has not been fully elucidated. Here, we show that Tax induces Bcl-3 expression, which in turn negatively regulates the Tax-induced NF-κB activation. Interestingly, both Bcl-3 up-regulation and NF-κB inhibition promote the autophagy process in HTLV-1-infected cells. Consistent with this, over-expression of Bcl-3 also results in enhancement of rapamycin-, pifithrin-α- or starvation-induced autophagy in control cells. Together, these data demonstrate that Bcl-3 acts as a negative regulator of NF-κB activation and promotes autophagy in HTLV-1-infected cells. •We confirmed that Tax and HTLV-1 viruses obviously induce Bcl-3 expression.•Bcl-3 negatively regulates NF-κB activation and transcription from HTLV-1 LTR.•Tax-induced NF-κB activation inhibits autophagy result from infection.•Tax and Bcl-3 could induce autophagy.•Bcl-3 enhances autophagy caused by certain autophagy inducer.