PROPERTIES OF THE HTLV I TAX PROTEIN

HTLV I Tax 蛋白的特性

• 批准号: 6376398
• 负责人: Noelle Sevilir Williams
• 金额: $ 24.67万
• 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: 1997-09-30 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6376398
• 关键词: HeLa cells; cAMP response element binding protein; enzyme mechanism; genetic library; genetic regulation; genetic regulatory element; genetic transcription; human T cell lymphotropic virus type 1; immunoaffinity chromatography; immunoprecipitation; intermolecular interaction; nuclear factor kappa beta; phosphorylation; virus genetics; virus protein; yeast two hybrid system

DESCRIPTION (adapted from applicant's abstract): HTLV-I Tax protein is critical for the activation of gene expression through both the CREB and NF-kB transcriptional pathways and is also responsible for the transformation of T-lymphocytes. Tax activates HTLV-I gene expression through three regulatory elements in the LTR known as the 21 bp repeats that contain binding sites for the ATF/CREB family. However, Tax will not activate gene expression from cellular promoters containing CRE elements, indicating that the overall structure of the 21 bp repeats is critical for its activation. Tax also activates gene expression via NF-kB binding sites and increases the gene expression of specific cellular genes. Dr. Gaynor's studies indicate that direct interactions between CREB and Tax result in the formation of a stable complex on the 21 bp repeats which markedly increases the recruitment of the coactivator CBP. CBP binds to a number of different cellular regulatory proteins including CREB and it is likely involved in bridging factors bound to upstream control elements with components of the basal transcription complex. Recent studies also indicate that CBP can directly interact with NF-kB proteins. Tax activation via NF-kB binding sites is potentially mediated through both direct or indirect interactions of Tax with NF-kB proteins and by Tax activation of cellular kinases that phosphorylate IkB resulting in its degradation and the constitutive nuclear expression of NF-kB. Four specific aims are proposed to extend these studies and to characterize cellular factors that modulate Tax function in an effort to determine its mechanism of action. The aims are: (1) to identify cellular factors that associate with Tax, (2) to determine the function of those factors, (3) to analyze how CBP modulates Tax activation via CREB and NF-kB pathways, and (4) to determine how Tax modulates the activity of kinases that phosphorylate IkB. The overall objective is to increase understanding of the mechanism of Tax transcriptional activation and transformation.

描述（改编自申请人摘要）：HTLV-I Tax蛋白为

项目成果

I-kappa B kinases alpha and beta have distinct roles in regulating murine T cell function.

I-kappa B 激酶 α 和 β 在调节小鼠 T 细胞功能中具有不同的作用。

• DOI: 10.4049/jimmunol.168.8.3721
• 发表时间: 2002
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Ren,Hong;Schmalstieg,Aurelia;vanOers,NicolaiSC;Gaynor,RichardB
• 通讯作者: Gaynor,RichardB

Sulindac enhances tumor necrosis factor-alpha-mediated apoptosis of lung cancer cell lines by inhibition of nuclear factor-kappaB.

Sulindac 通过抑制核因子-κB 增强肿瘤坏死因子-α 介导的肺癌细胞系凋亡。

• 发表时间: 2002
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research.
• 作者: Berman,KevinS;Verma,UditN;Harburg,Gwyndolen;Minna,JohnD;Cobb,MelanieH;Gaynor,RichardB
• 通讯作者: Gaynor,RichardB

Identification and validation of genes involved in the pathogenesis of colorectal cancer using cDNA microarrays and RNA interference.

• 发表时间: 2003-03
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: N. Williams;R. Gaynor;S. Scoggin;U. Verma;T. Gokaslan;C. Simmang;J. Fleming;Denise Tavana;E. Fren