Supplement to Support Research Training in HDAC11 and Cancer

支持 HDAC11 和癌症研究培训的补充品

• 批准号: 10380397
• 负责人: Rong Li
• 金额: $ 7.29万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10380397
• 关键词: Acylation; Alternative Splicing; Cancer Model; Cell Line; Chromatin; Deacetylase; Epigenetic Process; Excision; Exhibits; Gene Expression Regulation; Genes; Grant; HDAC11 gene; HDAC4 gene; Histone Deacetylase; Histones; Immune; Infiltration; Interferons; Knowledge; Lymphoma; Lysine; Malignant Neoplasms; Messenger RNA; Modeling; Mus; Nuclear; Oncogenes; Parents; Proteins; RNA Splicing; Regulation; Research Support; Research Training; Signal Transduction; Testing; Tumor Immunity; Work; amidase; cancer cell; cancer therapy; cell motility; chromatin modification; inhibitor/antagonist; parent grant; response; therapeutic target

Project Summary The histone deacetylaces (HDACs) are originally discovered as critical epigenetic regulators implicated in a wide range of cancers. HDACs are most associated with their namesake deacetylase activity; they catalyze the removal of acetyl groups from lysine residues, which typically condenses chromatin and decreases expression of certain genes. However, there is increasing evidence that many HDACs exhibit other enzymatic functions such as defatty-acylase activity. Additionally, HDACs have been illustrated to interact with proteins other than histones; HDAC11 was previously illustrated to functionally interact with RNA splicing machinery. Thus, the enzymatic mechanism(s) and target proteins of HDACs are not fully understood. In supplement to our Parent R01 grant aimed at studying HDAC11 in lymphoma, we strive to investigate HDAC11 defatty-acylation in RNA splicing. Defatty-acylation can direct the localization of proteins, and HDAC11 functions more efficiently as a cytosolic defatty-acylase than as a nuclear deacetylase. Therefore, our aim is to identify HDAC11 proximate proteins in cancer cells, pinpoint the function of HDAC11 defatty-acylation, and identify alternatively spliced mRNAs in response to HDAC11 disruption. The proposed work will advance understanding of HDAC11 in cancer gene regulation, contribute to growing knowledge of diverse HDAC functions, and potentially open new avenues for HDAC dependent cancer therapies.

项目摘要 组蛋白脱乙酰基面积（HDAC）最初被发现为涉及的关键表观遗传调节剂 在广泛的癌症中。 HDAC与它们的同名脱乙酰基酶活性最相关。他们 催化从赖氨酸残基中去除乙酰基，通常凝结染色质和 降低某些基因的表达。但是，越来越多的证据表明许多HDAC都表现出其他 酶函数，例如缺乏隔离酶活性。此外，已经说明了HDAC与 除组蛋白以外的蛋白质；先前说明了HDAC11与RNA剪接在功能上相互作用 机械。因此，HDAC的酶促机理和靶蛋白尚未完全了解。 为了补充我们的父r01赠款，旨在研究淋巴瘤的HDAC11，我们努力 研究RNA剪接中的HDAC11脱酰化。缺陷酰化可以指导蛋白质的定位， 与核脱乙酰基酶相比，HDAC11作为胞质缺乏酰化地带的发挥作用更有效。 因此，我们的目的是鉴定癌细胞中近端蛋白的HDAC11，查明HDAC11的功能 缺乏酰基化，并确定响应HDAC11中断的剪接的mRNA。提议 工作将提高对癌症基因调节中HDAC11的了解，有助于越来越多的知识 HDAC功能的多样化，并有可能为HDAC依赖性癌症疗法开放新途径。