title: Bcl-3, induced by Tax and HTLV-1, inhibits NF-κB activation and promotes autophagy.
abstract: 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.
authors.affiliation: Research Center for Immunology, Department of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China.
authors.forename: Jinheng
authors.initials: J
authors.lastname: Wang
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Niu
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.forename: Cai
authors.initials: C
authors.lastname: Gao
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Jingxian
authors.initials: J
authors.lastname: Han
authors.forename: Junying
authors.initials: J
authors.lastname: Li
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Gao
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhu
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Song
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Qin
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D001343:Autophagy; D000081242:B-Cell Lymphoma 3 Protein; D015972:Gene Expression Regulation, Neoplastic; D016356:Gene Products, tax / Q000276:immunology*; D015490:HTLV-I Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology* / Q000821:virology; D016328:NF-kappa B / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D015533:Transcriptional Activation
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D016356:Gene Products, tax; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors
keywords: Autophagy; Bcl-3; HTLV-1; NF-κB activation; Tax