TFIIB Autoacetylation in Transcription Initiation

转录起始中的 TFIIB 自乙酰化

• 批准号: 6892321
• 负责人: CHU H CHOI
• 金额: $ 4.99万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-11 至 2006-04-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6892321
• 关键词: DNA directed RNA polymerase; acetyl coA; acetylation; genetic regulation; genetic transcription; intermolecular interaction; postdoctoral investigator; posttranslational modifications; protein structure; protein structure function; transcription factor

DESCRIPTION (provided by applicant): A novel autoacetylation in the general transcription factor lIB has been discovered, a specific transfer of the acetyl group in acetyl coenzyme A to TFIIB. Not only is this autocatalytic activity novel for any transcription factor is the acetylation of TFIIB drastically alters transcriptional function both in vitro and in cells. The interaction between TFIIB and TFIIF is stabilized by the acetylation of lysine 238 of TFIIB. This system, then, is important for study on two levels. First, the impact of acetylation of TFIIB on transcriptional activity suggests that it may act as a new regulatory pathway for polymerase II transcription. It is proposed to study further the changed interaction of TFIIB and TFIIF, to map out the interaction surface and better define the effects of acetyl-TFllB on the preinitiation transcriptional complex. Secondly, it is proposed to define a mechanism for the autoacetylation of TFIIB using structural and chemical analysis of the interaction between acetyI-CoA and TFIIB. Understanding this novel regulation of transcription may eventually shed light on disease and have applications in gene therapy.

描述（由申请人提供）： 在一般转录因子IIB中发现了一种新的自乙酰化，乙酰辅酶A中的乙酰基特异性转移到TFIIB。这种自催化活性不仅对于任何转录因子都是新颖的，而且TFIIB的乙酰化在体外和细胞中都显著改变了转录功能。TFIIB和TFIIF之间的相互作用通过TFIIB的赖氨酸238的乙酰化而稳定。 因此，这一系统对于两个层面的研究很重要。首先，TFIIB的乙酰化对转录活性的影响表明它可能作为聚合酶II转录的新的调节途径。 建议进一步研究TFIIB和TFIIF相互作用的变化，绘制相互作用表面，更好地确定乙酰基-TFIIB对前起始转录复合物的影响。其次，提出了使用乙酰辅酶A和TFIIB之间的相互作用的结构和化学分析来定义TFIIB的自动乙酰化的机制。了解这种新的转录调控可能最终揭示疾病，并在基因治疗中有应用。