TAT ASSOCIATED KINASE REGULATION OF HIV GENE EXPRESSION

HIV 基因表达的 TAT 相关激酶调节

• 批准号: 6170801
• 负责人: Richard B Gaynor
• 金额: $ 22.91万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6170801
• 关键词: DNA directed RNA polymerase; adenosinetriphosphatase; enzyme activity; gene expression; helicase; host organism interaction; human immunodeficiency virus 1; human tissue; phosphotransferases; transcription factor; virus protein

DESCRIPTION: (Adapted From Investigator's Abstract) Tat stimulates gene expression by increasing the ability of RNA polymerase II to efficiently undergo transcriptional elongation. Recent studies suggest that tat can bind a cellular kinase that phosphorylates the C-terminal domain (CTD) of RNA polymerase II. The investigator has purified the kinase complex and demonstrated that it contains novel components as well as previously characterized components of the multi-protein transcription factor, TF II H. Wildtype, but not mutant tat proteins, greatly enhance the ability of the kinase complex to phosphorylate the RNA polymerase II CTD and addition of the kinase to in vitro transcription assays with the HIV-1 LTR markedly stimulated tat activation, suggesting that tat-associated kinase complex is a critical cellular factor involved in tat activation of HIV-1. The investigator proposes to examine the mechanism by which tat association with a kinase complex increases HIV-1 gene expression. Specific aims include: Determine which cellular components of the kinase complex are able to directly associate with tat. Assay the function of novel components of the tat-associated complex using both in vitro and in vivo assays. Determine whether tat facilitates association of the kinase complex with RNA polymerase II and whether tat alters enzymatic activities of TF II H. Develop a reconstituted in vitro transcription system in which tat activation is dependent on the addition of the tat-associated kinase and further to determine the role of this kinase on regulating in vivo HIV-1 gene expression.

描述：（改编自研究者摘要）Tat刺激基因