SPECIFICITY OF UBIQUITINATION--THE HPV E6/E6 AP PARADIGM

泛素化的特异性——HPV E6/E6 AP 范式

• 批准号: 6361396
• 负责人: JON HUIBREGTSE
• 金额: $ 7.35万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-13 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6361396
• 关键词: Saccharomyces cerevisiae; acid aminoacid ligase; enzyme activity; human papillomavirus; microorganism culture; oligonucleotides; p53 gene /protein; site directed mutagenesis; tumor suppressor proteins; ubiquitin; virus genetics; virus protein

DESCRIPTION: E6-AP (E6-Associated Protein) is a cellular protein that associates with and catalyzes ubiquitination of p53 in anE6-dependent manner. Characterization of E6-AP showed it to be representative of a large family of ubiquitin-protein ligases (or E3 proteins), which have been postulated to play the major role in substrate selectivity. The applicant proposes a model for function of the E6-AP-related E3 proteins which states that they consist of two broad domains: an N-terminal substrate recognition domain, and a C-terminal catalytic domain (the hect domain, for homologous to E6-AP C-terminus) which ubiquitinates bound substrates. The specific aims of this proposal are: 1) to evaluate this model by determining if substrate specificity can be redirected by substitution of N-terminal sequences and if hect domains are functionally interchangeable among E3 proteins, 2) to evaluate this model with respect to E6-AP by precisely mapping the determinants necessary for p53 association and hect domain function, and 3) to identify substrates of Rsp5, an essential yeast hectE3, beginning with predictions of the 2-domain model and taking a combined genetic and biochemical approach. The long-term objectives of this application are to understand the mechanisms of action of the hect E3 proteins and their role, as well as the role of the high-risk HPV E6 proteins (and possible cellular analogs), in directing the specificity of the ubiquitin system. The ultimate goal is a more complete understanding of HPV-associated carcinogenesis and other processes regulated by protein ubiquitination.

描述：E6-AP （E6-Associated Protein）是一种细胞蛋白