HTLV-1 bZIP factor suppresses the centromere protein B (CENP-B)-mediated trimethylation of histone H3K9 through the abrogation of DNA-binding ability of CENP-B

Abstract

Human T-cell leukaemia virus type-1 (HTLV-1) infection causes adult T-cell leukaemia (ATL). The viral protein HTLV-1 bZIP factor (HBZ) is constitutively expressed in ATL cells, suggesting that HBZ plays a major role in the pathogenesis of HTLV-1-associated disease. Here, we identified centromere protein B (CENP-B) as a novel interacting partner of HBZ. HBZ and CENP-B associate with their central regions in cells. Furthermore, overexpression of HBZ abrogated the DNA-binding activity of CENP-B to the a-satellite DNA region containing the CENP-B box motif, which in turn inhibited the CENP-B-mediated trimethylation of histone H3K9 in T-cells.

Multifaceted functions and roles of HBZ in HTLV-1 pathogenesis

“…The major pathways that these interactions have impact on, either positive (+) or negative (−), are noted close to respective cellular proteins while more detailed description can be found in the text. Some of the interactions are not discussed in the text due to space limitations, which include 26s proteasome [ 93 ], CENP-B [ 94 ], C/EBPα [ 95 ] and IRF-1 [ 96 ]. For Foxp3, HBZ enhances transcription from the Foxp3 promoter (Treg differentiation: diff.)…”

Role of Virus-Induced Host Cell Epigenetic Changes in Cancer

“…Mukai and Ohshima demonstrated that HBZ interacted with centromere protein B (CENP-B), a protein that enhances H3K9me3 by recruiting the histone methyltransferase KMT1A/SUV39H1. The interaction between HBZ and CENP-B impaired recruitment of KMT1A and significantly reduced the amount of H3K3me3 [ 154 ]. Transcription of the BCL2 like 11 ( BCL2L11 ) gene, which encodes the proapoptotic protein BCL2 interacting mediator of cell death (BIM), was decreased in ATL cells compared to HTLV-negative T cell lines and normal PBMC.…”