Wnt信号通路
生物
LRP5
转录因子
LRP6型
连环蛋白
增强子
细胞生物学
白血病
细胞生长
信号转导
癌症研究
遗传学
基因
作者
Guangyong Ma,Jun‐ichirou Yasunaga,Jun Fan,Shin-ichi Yanagawa,Masao Matsuoka
出处
期刊:Oncogene
[Springer Nature]
日期:2012-10-08
卷期号:32 (36): 4222-4230
被引量:62
摘要
Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL). HTLV-1 bZIP factor (HBZ), the viral gene transcribed from the antisense strand, is consistently expressed in ATL cells and promotes their proliferation. In this study, we found that a Wnt pathway-related protein, disheveled-associating protein with a high frequency of leucine residues (DAPLE), interacts with both HTLV-1 Tax and HBZ. In the presence of DAPLE, Tax activated canonical Wnt signaling. Conversely, HBZ markedly suppressed canonical Wnt activation induced by either Tax/DAPLE or β-catenin. As a mechanism of HBZ-mediated Wnt suppression, we found that HBZ targets lymphoid enhancer-binding factor 1, one of the key transcription factors of the pathway, and impairs its DNA-binding ability. We also observed that the canonical Wnt pathway was not activated in HTLV-1-infected cells, whereas the representative of noncanonical Wnt ligand, Wnt5a, which antagonizes canonical Wnt signaling, was overexpressed. HBZ was able to induce Wnt5a transcription by enhancing its promoter activity through the TGF-β pathway. Importantly, knocking down of Wnt5a in ATL cells repressed cellular proliferation and migration. Our results implicate novel roles of HBZ in ATL leukemogenesis through dysregulation of both the canonical and noncanonical Wnt pathways.
科研通智能强力驱动
Strongly Powered by AbleSci AI