Disruption of transcription network of cellular genes by human T-cell leukemia virus type-1.

人类 T 细胞白血病病毒 1 型对细胞基因转录网络的破坏。

• 批准号: 22501000
• 负责人: OHSHIMA Takayuki
• 金额: $ 2.33万
• 依托单位: Tokushima Bunri University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22501000/
• 关键词: ウイルス; HTLV-1; 転写制御; HBZ; 発がん; オートファジー; 細胞死; 薬学; 遺伝子; 応用微生物; SUMO化修飾; 翻訳後修飾

Human T-cell leukemia virus type-1 (HTLV-1) infection causes adult T-cell leukemia (ATL). Modulation of the transcriptional control of cellular genes by HTLV-1 is thought to be associated with the development of ATL. The viral protein HTLV-1 basic leucine-zipper factor (HBZ) has been shown to dysregulate the activity of cellular transcription factors. We evidence that HBZ reduced both IRF-1 DNA-binding activity and stability via a proteasome-dependent pathway. In addition, IRF-1-mediated apoptosis is significantly reduced by ectopic production of the HBZ. Also, we demonstrate that HBZ is exported from the nucleus to the cytoplasm, where it activates the mTOR signaling pathway through an association with growth arrest and DNA damage gene 34 (GADD34). Starvation-induced autophagy is significantly suppressed by the overexpression of HBZ.

人类T细胞白血病病毒1型(HTLV-1)感染导致成人T细胞白血病(ATL)。HTLV-1对细胞基因转录调控的调控被认为与ATL的发生有关。病毒蛋白HTLV-1碱性亮氨酸拉链因子(HBZ)可失调细胞转录因子的活性。我们的证据表明，HBZ通过蛋白酶体依赖的途径降低了IRF-1DNA结合活性和稳定性。此外，异位产生的HBZ显著减少了IRF-1介导的细胞凋亡。此外，我们还证明了HBZ从细胞核输出到细胞质，在那里它通过与生长停滞和DNA损伤基因34(Gadd34)相关的方式激活mTOR信号通路。HBZ的过表达显著抑制了饥饿诱导的自噬。

项目成果

Protein inhibitor of activated STAT, PIASy regulates alpha-smooth muscle actin expression by interacting with E12 inmesangial cells.

PIASy 是激活 STAT 的蛋白质抑制剂，通过与系膜细胞中的 E12 相互作用来调节 α-平滑肌肌动蛋白的表达。

• 发表时间: 2012
• 期刊: PLoS One
• 影响因子: 3.7
• 作者: Kazuo Torikoshi;Hideharu Abe;Takeshi Matsubara;Takahiro Hirano;Takayuki Ohshima;Taichi Murakami;Makoto Araki;Akira Mima;Noriyuki Iehara;Atsushi Fukatsu;Toru Kita;Hideyuki Arai;and Toshio Doi.
• 通讯作者: and Toshio Doi.

mTORシグナルの活性化におけるHTLV-1HBZタンパク質の役割

HTLV-1HBZ蛋白在mTOR信号激活中的作用

• 发表时间: 2010
• 作者: 向井理紗;大島隆幸
• 通讯作者: 大島隆幸

HTLV-1 Basic Leucine-Zipper Factor, HBZ, Interacts With MafB and Suppresses Transcription Through a Maf Recognition Element

• DOI: 10.1002/jcb.22687
• 发表时间: 2010-09-01
• 期刊: JOURNAL OF CELLULAR BIOCHEMISTRY
• 影响因子: 4
• 作者: Ohshima, Takayuki;Mukai, Risa;Shimotohno, Kunitada
• 通讯作者: Shimotohno, Kunitada

Ubiquitination-mediated degradation and DNA-binding impairment of IRF-1 were induced by HTLV-1 HBZ

HTLV-1 HBZ 诱导泛素化介导的 IRF-1 降解和 DNA 结合损伤

• 发表时间: 2011
• 作者: Risa Mukai;and Takayuki Ohshima.
• 通讯作者: and Takayuki Ohshima.

Dual effects of HTLV-1 bZIP factor in suppression of interferon regulatory factor 1

• DOI: 10.1016/j.bbrc.2011.05.014
• 发表时间: 2011-06-03
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Mukai, Risa;Ohshima, Takayuki
• 通讯作者: Ohshima, Takayuki