title: 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.
authors.affiliation: Henan Medical College, Zhengzhou, Henan 451191, P.R. China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Henan Medical College, Zhengzhou, Henan 451191, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Henan Medical College, Zhengzhou, Henan 451191, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Henan Medical College, Zhengzhou, Henan 451191, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Qian
authors.affiliation: Henan Medical College, Zhengzhou, Henan 451191, P.R. China.
authors.forename: Xianmei
authors.initials: X
authors.lastname: Song
authors.affiliation: Henan Medical College, Zhengzhou, Henan 451191, P.R. China.
authors.forename: Xueyin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Henan Medical College, Zhengzhou, Henan 451191, P.R. China.
authors.forename: Chaokuan
authors.initials: C
authors.lastname: Yang
authors.affiliation: School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhao
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D019938:Cyclin D1 / Q000235:genetics*; D005786:Gene Expression Regulation; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D016350:Leucine Zippers; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D012191:Retroviridae Proteins / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C479751:HBZ protein, human T-cell leukemia virus type I; D016328:NF-kappa B; D012191:Retroviridae Proteins; D019938:Cyclin D1