Function of Protein Methylation in Chromatin and Signaling Regulation
蛋白质甲基化在染色质中的功能和信号传导调控
基本信息
- 批准号:10339323
- 负责人:
- 金额:$ 66.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-01 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:BiochemicalBiological ProcessBiologyCell modelCell physiologyCellular biologyChromatinDiseaseEnzymesEpigenetic ProcessGene ExpressionGenomicsGoalsHealthHistidineHistone H3HomeostasisHumanHuman GenomeLinkLysineMalignant NeoplasmsMammalian CellMethylationMethyltransferaseModificationMolecularMutationPathogenesisPathologyPhysiologicalPlayPost-Translational Protein ProcessingPost-Translational RegulationProtein MethylationProtein MethyltransferasesProteinsProteomicsRegulationResearchRoleSignal PathwaySignal TransductionSourceclinically actionablegene translocationhistone methylationhuman diseaseinsightmouse modelmultidisciplinarynon-histone proteinprotein function
项目摘要
ABSTRACT
Covalent post-translational protein modifications (PTMs) contribute to all aspects of cell physiology and are a
major source of protein functional diversity in mammalian cells. Aberrant regulation of PTMs is a common
feature of human diseases. Our research focuses on two important PTMs: protein methylation at lysine and
histidine residues. Our overarching goal is to elucidate at a molecular level the physiologic roles for lysine and
histidine methylation signaling in the regulation of chromatin biology, epigenetics and other fundamental
biological processes, and to understand how disruption in these mechanisms contributes to human disease.
Within this research framework we will investigate the biology and function of enzymes that regulate histone
methylation dynamics, with a focus on methylation at histone H3 lysine 36 (H3K36). Beyond histone
methylation, there is a growing appreciation that a number of non-histone proteins, including several with clear
roles in gene expression and signal transduction are lysine methylated. Indeed, there are likely far greater than
one hundred lysine methyltransferases in the human genome, and an increasing number of examples of
mutation or translocation of these genes being linked to human disorders. Thus, it is likely that deregulation in
non-histone protein methylation homeostasis plays a crucial role in disease pathogenesis. We will explore the
biology and function of new enzymes and non-histone protein methylation signaling pathways. In addition to
lysine methylation, other residues like histidine are also methylated; though relatively little is known about the
histidine methylation modification network. We will explore the hypothesis that protein histidine methylation has
an underappreciated and significant role in signal transduction, cell biology, and disease pathogenesis. For our
studies, we will use a multi-disciplinary strategy that include biochemical, molecular, proteomic, genomic,
cellular and mouse modeling approaches.
摘要
共价翻译后蛋白修饰(PTM)有助于细胞生理学的各个方面,是一种
哺乳动物细胞中蛋白质功能多样性的主要来源。PTMS的异常调节是一种常见的现象
人类疾病的特征。我们的研究集中在两个重要的PTMS上:赖氨酸和蛋白质甲基化
组氨酸残留物。我们的首要目标是在分子水平上阐明赖氨酸和赖氨酸的生理作用。
组氨酸甲基化信号在染色质生物学、表观遗传学等基础调控中的作用
生物过程,并了解这些机制的破坏如何导致人类疾病。
在这个研究框架内,我们将研究调节组蛋白的酶的生物学和功能。
甲基化动力学,重点是组蛋白H3赖氨酸36(H3K36)的甲基化。超越组蛋白
甲基化后,人们越来越认识到,一些非组蛋白蛋白,包括几个具有明确
赖氨酸甲基化在基因表达和信号转导中起着重要作用。事实上,有可能远远超过
人类基因组中的100个赖氨酸甲基转移酶,以及越来越多的
这些基因的突变或易位与人类疾病有关。因此,放松管制很可能是
非组蛋白甲基化动态平衡在疾病发病机制中起着至关重要的作用。我们将探索
新的酶和非组蛋白甲基化信号通路的生物学和功能。除了……之外
赖氨酸甲基化,其他残基,如组氨酸,也是甲基化的;尽管对
组氨酸甲基化修饰网络。我们将探索蛋白质组氨酸甲基化具有
在信号转导、细胞生物学和疾病发病机制中被低估和重要的作用。为我们的
研究,我们将使用多学科策略,包括生化,分子,蛋白质组,基因组,
细胞和鼠标建模方法。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Or P. Gozani', 18)}}的其他基金
Therapeutic Targeting of NSD2 in Lung Adenocarcinoma
NSD2 在肺腺癌中的治疗靶向
- 批准号:
10657069 - 财政年份:2023
- 资助金额:
$ 66.74万 - 项目类别:
Role of NSD3 in regulation of cancer pathogenesis
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10633579 - 财政年份:2023
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$ 66.74万 - 项目类别:
Function of Protein Methylation in Chromatin and Signaling Regulation
蛋白质甲基化在染色质中的功能和信号传导调控
- 批准号:
10580699 - 财政年份:2021
- 资助金额:
$ 66.74万 - 项目类别:
Role of the METTL13 Lysine Methyltransferase in Signaling and Cancer
METTL13 赖氨酸甲基转移酶在信号传导和癌症中的作用
- 批准号:
9761687 - 财政年份:2019
- 资助金额:
$ 66.74万 - 项目类别:
Unnatural Amino Acid Chemistry for Lysine Methyltransferase Substrate Discovery
赖氨酸甲基转移酶底物发现的非天然氨基酸化学
- 批准号:
9808782 - 财政年份:2019
- 资助金额:
$ 66.74万 - 项目类别:
Unnatural Amino Acid Chemistry for Lysine Methyltransferase Substrate Discovery
赖氨酸甲基转移酶底物发现的非天然氨基酸化学
- 批准号:
10006583 - 财政年份:2019
- 资助金额:
$ 66.74万 - 项目类别:
Role of the METTL13 Lysine Methyltransferase in Signaling and Cancer
METTL13 赖氨酸甲基转移酶在信号传导和癌症中的作用
- 批准号:
10569626 - 财政年份:2019
- 资助金额:
$ 66.74万 - 项目类别:
Role of the METTL13 Lysine Methyltransferase in Signaling and Cancer
METTL13 赖氨酸甲基转移酶在信号传导和癌症中的作用
- 批准号:
10338153 - 财政年份:2019
- 资助金额:
$ 66.74万 - 项目类别:
Role of the METTL13 Lysine Methyltransferase in Signaling and Cancer
METTL13 赖氨酸甲基转移酶在信号传导和癌症中的作用
- 批准号:
10116173 - 财政年份:2019
- 资助金额:
$ 66.74万 - 项目类别:
Regulation of Signaling by Histidine Protein Methylation
组氨酸蛋白甲基化对信号传导的调节
- 批准号:
9974541 - 财政年份:2019
- 资助金额:
$ 66.74万 - 项目类别:
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