Research on Gene Expression Network via histone acetylation
Research on Gene Expression Network via histone acetylation
批准号:
11470036
负责人:
ISHII Shunsuke
金额:
$9.22万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B).
财政年份:
1999
资助国家:
日本
项目状态:
已结题
起止时间:
1999 至 2000
中文摘要
ski基因最初被确定为致癌基因。我们已经证明c-ski原癌基因产物(c-ski)直接与协同抑制因子N-CoR和mSin3A结合,并与组蛋白去乙酰化酶(HDAC)形成复合物。c-Ski作为协同抑制因子,是肿瘤抑制因子Mad和Rb以及核激素受体介导的转录抑制所必需的。我们已经产生了缺乏雪(滑雪相关的新)基因的突变小鼠,该基因编码滑雪相关基因。在胚胎早期发育过程中,一氧化氮对囊胚的形成至关重要,缺乏一氧化氮的胚胎在发育早期死亡。这些杂合突变体看起来是健康的,但在他们身上观察到自发产生的肿瘤。此外,当他们接受化学致癌物DMBA治疗时,他们对肿瘤发生的易感性增加。在ski杂合突变小鼠中也得到了类似的结果。这些结果表明,根据细胞环境的不同,ski和snow基因可以作为致癌基因或肿瘤抑制基因。我们还产生了缺乏CBP的突变小鼠,CBP是最著名的含有组蛋白乙酰化酶活性的共激活剂。由于脑出血,cbp缺陷胚胎在E12.5-E14.5死亡。出血是由血管形成受损引起的,说明CBP在血管形成中的重要作用。cbp缺陷胚胎的肝脏造血功能也出现部分受损。我们发现CBP直接使c-Myb乙酰化,而c-Myb的乙酰化增强了c-Myb与CBP的关联。这是CBP调控转录因子活性的一个有趣的新机制。
英文摘要
The ski gene was originally identified as an oncogene. We have demonstrated that c-ski proto-oncogene product (c-Ski) directly associates with co-repressors N-CoR and mSin3A and forms a complex with histone deacetylase (HDAC). c-Ski acts as a co-repressor, and is required for transcriptional repression mediated by tumor suppressors, Mad and Rb, and nuclear hormone receptors . We have generated the mutant mice lacking the sno (ski-related novel) gene, which encodes the ski-related gene. Sno is essential for blastocyst formation in early development, and the sno-deficient embryos die at an early stage of development. The sno heterozygous mutants appeared to be healthy, but spontaneously arisen tumors were observed in them. Furthermore, they have the increased susceptibility to tumorigenesis when they were treated with the chemical carcinogen DMBA.Similar results were also obtained with the ski heterozygous mutant mice. These results indicate that ski and sno genes act as either oncogene or tumor suppressor depending on the cellular context. We also generated the mutant mice lacking CBP, which is the most famous co-activator containing the histone acetylase activity. The Cbp-deficient embryos died at E12.5-E14.5 due to hemorrhage in the brain. Hemorrhage was caused by impaired formation of blood vessel, indicating the important role of CBP for blood vessel formation. The Cbp-deficient embryos also exhibited the partially impaired hematopoesis in fetal liver. We have found that CBP directly acetylates c-Myb, and acetylation of c-Myb enhances the association between c-Myb and CBP.This is an interesting novel mechanism by which co-activator CBP regulates the activity of transcription factor.
期刊论文(45)
专著(0)
科研奖励(0)
会议论文
登录
查看更多内容
野村照明 他: "Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor." Genes Dev.13. 412-423 (1999)
Shomei Nomura 等人:“Ski 是 Mad 和甲状腺激素受体转录抑制所需的组蛋白脱乙酰酶复合物的组成部分。”Genes Dev.13 (1999)。
DOI:
--
发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
佐野祐治他: "ATF-2 is a common nuclear target of Smad and TAK1 pathways in TGF-β signaling"J.Biol.Chem.. 274. 8949-8957 (1999)
Yuji Sano 等人:“ATF-2 是 TGF-β 信号传导中 Smad 和 TAK1 途径的常见核靶点”J.Biol.Chem.. 274. 8949-8957 (1999)
DOI:
--
发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
時任文乃 他: "Viral-Ski inhibits retinoblastoma protein(Rb)-mediated transcriptional repression in a dominant negative fashion." J.Biol.Chem.274. 4485-4488 (1999)
Fumino Tokito 等人:“Viral-Ski 以显性负性方式抑制视网膜母细胞瘤蛋白 (Rb) 介导的转录抑制。”J.Biol.Chem.274 (1999)。
DOI:
--
发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
Tahirov,T.H. 他: "Structural analyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBFβ."Cell. (印刷中). (2001)
Tahirov, T.H. 等人:“AML1/Runx-1 Runt 结构域的 DNA 识别及其 CBFβ 的变构控制的结构分析”(正在出版)。
DOI:
--
发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
Toshie SHINAGAWA et al.: "The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice."EMBO J.. 19. 2280-2291 (2000)
Toshie SHINAGAWA 等人:“sno 基因编码组蛋白脱乙酰酶复合物的一个组成部分,在小鼠中充当肿瘤抑制因子。”EMBO J.. 19. 2280-2291 (2000)
DOI:
--
发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
共 19 条
Change of telomere length by stress
-
批准号:24657008
-
项目类别:Grant-in-Aid for Challenging Exploratory Research
-
资助金额:$2.58万
-
财政年份:2012
-
负责人:ISHII Shunsuke
-
依托单位:
Regulation of metabolism and cellular proliferation by virus infection
-
批准号:23659244
-
项目类别:Grant-in-Aid for Challenging Exploratory Research
-
资助金额:$2.58万
-
财政年份:2011
-
负责人:ISHII Shunsuke
-
依托单位:
Research on signal transduction via transcriptional mediators
-
批准号:23370079
-
项目类别:Grant-in-Aid for Scientific Research (B)
-
资助金额:$12.81万
-
财政年份:2011
-
负责人:ISHII Shunsuke
-
依托单位:
Research on transcriptional mediators regulated by signals
-
批准号:20370074
-
项目类别:Grant-in-Aid for Scientific Research (B)
-
资助金额:$13.06万
-
财政年份:2008
-
负责人:ISHII Shunsuke
-
依托单位:
Transcriptional control by mediators and their physiological significance
-
批准号:14002011
-
项目类别:Grant-in-Aid for Specially Promoted Research
-
资助金额:$380.22万
-
财政年份:2002
-
负责人:ISHII Shunsuke
-
依托单位:
Research on Gene Expression Network via histone acetylation
-
批准号:12557018
-
项目类别:Grant-in-Aid for Scientific Research (B)
-
资助金额:$8.32万
-
财政年份:2000
-
负责人:ISHII Shunsuke
-
依托单位:
Research on Gene Expression Network via Coactivator CBP
-
批准号:09470037
-
项目类别:Grant-in-Aid for Scientific Research (B)
-
资助金额:$8.13万
-
财政年份:1997
-
负责人:ISHII Shunsuke
-
依托单位:
Target genes and biological role of transcription factors in animal
-
批准号:09277103
-
项目类别:Grant-in-Aid for Scientific Research on Priority Areas (A)
-
资助金额:$196.99万
-
财政年份:1997
-
负责人:ISHII Shunsuke
-
依托单位:
Analysis of physiological role of transcriptional regulators using gene knock out mice
-
批准号:06454172
-
项目类别:Grant-in-Aid for General Scientific Research (B)
-
资助金额:$4.48万
-
财政年份:1994
-
负责人:ISHII Shunsuke
-
依托单位:
Regulation of transcription factors by protein-protein interaction
-
批准号:04454161
-
项目类别:Grant-in-Aid for General Scientific Research (B)
-
资助金额:$3.9万
-
财政年份:1992
-
负责人:ISHII Shunsuke
-
依托单位:
Regulation of transcriptional factors by phosphorylation
-
批准号:02454149
-
项目类别:Grant-in-Aid for General Scientific Research (B)
-
资助金额:$3.97万
-
财政年份:1990
-
负责人:ISHII Shunsuke
-
依托单位:
国内基金
海外基金
登录
查看更多内容
LECT2通过CBP/FOXO1轴调控内皮细胞周期参与心肌梗死后血管新生的机制研究
-
批准号:2026JJ60628
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:邹普
-
依托单位:
MSC衍生的外泌体通过p300/CBP乳酸化抑制NEDD4/ESM1泛素化调节脂质代谢抑制AS进展的作用及机制研究
-
批准号:2026JJ82430
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:符孝磊
-
依托单位:
CBP/p300降解剂的成药性优化及抗白血病活性研究
-
批准号:
-
项目类别:省市级项目
-
资助金额:10.0万元
-
批准年份:2025
-
负责人:胡建康
-
依托单位:
左金丸调控p300/CBP介导的CSNK2A1组蛋白乳酸化逆转胃癌化疗耐药的机制研究
-
批准号:--
-
项目类别:面上项目
-
资助金额:--
-
批准年份:2024
-
负责人:汤庆丰
-
依托单位:
融合蛋白MOZ-CBP/P300诱发急性髓系白血病的分子机制研究
-
批准号:
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2024
-
负责人:
-
依托单位:
氨基修饰加剧纳米聚苯乙烯跨代神经毒性及组蛋白乙酰转移酶CBP-1介导的分子调控机制
-
批准号:
-
项目类别:省市级项目
-
资助金额:15.0万元
-
批准年份:2024
-
负责人:王大勇
-
依托单位:
CBP调控TXNIP促进NLRP3炎症小体介导的巨噬细胞焦亡参与急性痛风性关节炎的机制研究
-
批准号:--
-
项目类别:地区科学基金项目
-
资助金额:--
-
批准年份:2024
-
负责人:毕潇文
-
依托单位:
CBP/p300-HADH轴在基础胰岛素分泌调节中的作用和机制研究
-
批准号:82370798
-
项目类别:面上项目
-
资助金额:49.00万元
-
批准年份:2023
-
负责人:王晓
-
依托单位:
铜暴露通过CBP/CREB/FDX1诱导海马神经元铜死亡的表观调控机制与作用研究
-
批准号:82373541
-
项目类别:面上项目
-
资助金额:49万元
-
批准年份:2023
-
负责人:尹立红
-
依托单位:
FBXL19与USP14双向调节室旁核CBP稳定在慢性应激致HPA轴亢奋进程中的效应研究
-
批准号:82371519
-
项目类别:面上项目
-
资助金额:47万元
-
批准年份:2023
-
负责人:江波
-
依托单位: