Excellence in Research: Crosstalk between the STK4/Hippo and NF-Kappa B pathway in mammalian cells

卓越研究：哺乳动物细胞中 STK4/Hippo 和 NF-Kappa B 通路之间的串扰

• 批准号: 1832022
• 负责人: Bekir Cinar
• 金额: $ 49.95万
• 依托单位: Clark Atlanta University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1832022&HistoricalAwards=false
• 关键词: Excellence; Research; Crosstalk; between; STK4

The goal of this project is to understand how molecular signals inside the cell are used to control cell size and growth, cell migration, and cell survival under changing environmental conditions. Using mammalian cells grown in culture, undergraduate and graduate students from an undergraduate institution that serves students from disproportionately underrepresented African-American communities will use a range of biochemical, molecular biology, genetics, and genomics approaches to determine how components from different signaling pathways communicate to coordinate cell growth. This project will provide undergraduate and graduate students with training and educational opportunities in biological sciences, allowing them to further pursue career goals in academia or in life sciences industries. Additionally, incorporation of research findings from this project into the classroom curriculum will further enhance their quality of education and research in life sciences, helping to reduce disparities in STEM employment by broadening participation in the Nation's STEM research workforce.This project will investigate the mechanism of the interaction between the YAP/TEAD protein, a key nuclear effector of the STK4/Hippo pathway, and RELA, a component of the NF-Kappa B (NFκB) transcription factors. The aims of this project are (a) to define the signaling mechanism that regulates YAP/TEAD and RELA interactions, (b) to determine the mechanism by which YAP/TEAD and RELA proteins physically interact in the cell, and (c) to demonstrate whether YAP/TEAD regulates the RELA-DNA interaction and the RELA-dependent gene transcription and cellular function. The techniques to be utilized in this project include high-throughput RNA or DNA sequencing, CRISPR/Cas9-aided genome editing, chromatin-immunoprecipitation and other molecular assays, and bioinformatics data analysis. The outcomes of this research include a comprehensive dissection of the mechanism of crosstalk between the STK4/Hippo and NFκB signaling in mammalian cells.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该项目的目标是了解细胞内的分子信号如何在不断变化的环境条件下控制细胞的大小和生长，细胞迁移和细胞存活。利用培养的哺乳动物细胞，来自一所本科院校的本科生和研究生将使用一系列生化、分子生物学、遗传学和基因组学方法来确定来自不同信号通路的成分如何沟通以协调细胞生长。该项目将为本科生和研究生提供生物科学方面的培训和教育机会，使他们能够在学术界或生命科学行业进一步追求职业目标。此外，将该项目的研究成果纳入课堂课程将进一步提高他们在生命科学方面的教育和研究质量，通过扩大美国STEM研究队伍的参与，帮助缩小STEM就业方面的差距。本项目将研究STK4/Hippo通路的关键核效应蛋白YAP/TEAD与NF-Kappa B （NF&#954；B）转录因子的组成部分RELA之间相互作用的机制。本项目的目的是(a)确定调控YAP/TEAD和RELA相互作用的信号机制，(b)确定YAP/TEAD和RELA蛋白在细胞中物理相互作用的机制，以及(c)证明YAP/TEAD是否调控RELA- dna相互作用以及RELA依赖基因的转录和细胞功能。本项目将使用的技术包括高通量RNA或DNA测序、CRISPR/ cas9辅助基因组编辑、染色质免疫沉淀等分子分析、生物信息学数据分析。本研究的结果包括对STK4/Hippo与NF&amp；#954；哺乳动物细胞中的B信号。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Regulation of the Hippo-YAP Signaling by Cytokines in Prostate Cancer Cell Lines

前列腺癌细胞系中细胞因子对 Hippo-YAP 信号传导的调节

• 发表时间: 2020
• 期刊: Georgia
• 作者: Seymour, Demaiya;Boston, Ava;Cinar, Bekir
• 通讯作者: Cinar, Bekir

Abstract P589: Crosstalk Between the Hippo-YAP and Nuclear Factor-Kappa B-RELA Signaling

摘要 P589：Hippo-YAP 与核因子-Kappa B-RELA 信号传导之间的串扰

• 发表时间: 2019
• 期刊: D.C.
• 作者: Cinar, B;Said-Bandy, E;Almathkour, M.M;Carlos, M.
• 通讯作者: Carlos, M.

The Hippo effector YAP1 biochemically and functionally interacts with the nuclear factor-kappa B/RELA transcription factor

Hippo效应子YAP1与核因子-kappa B/RELA转录因子在生化和功能上相互作用

• 发表时间: 2021
• 期刊: The FASEB journal
• 作者: Cinar, B: Al-Mathkour;Dwead, A;Boston, A;Alp, E.
• 通讯作者: Alp, E.

Abstract P2386: Androgen Receptor Signaling Promotes YAP1 Nuclear Localization

摘要 P2386：雄激素受体信号传导促进 YAP1 核定位

• 发表时间: 2019
• 期刊: ASCB-EMBO 2018 Annual Meeting
• 作者: Cinar, B: Al-Mathkour;Khan, S. and
• 通讯作者: Khan, S. and

The Transcriptional Coregulatory Protein YAP1 Interacts with RNA Binding Protein NPM1

转录核心调节蛋白 YAP1 与 RNA 结合蛋白 NPM1 相互作用

• 发表时间: 2022
• 期刊: Experimental Biology 2022 Annual Meeting
• 作者: Dwead, Abdulrahman;Al-Mathkour, Marwah;Cinar, Bekir
• 通讯作者: Cinar, Bekir