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Post-translational Modifications of High-mobility Group Proteins

高迁移率组蛋白的翻译后修饰

基本信息

批准号：
7882769
负责人：
Yinsheng Wang
金额：
$ 5.73万
依托单位：
UNIVERSITY OF CALIFORNIA RIVERSIDE
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7882769
关键词：
Acetylation Adopted Affect Amino Acids Apoptosis Binding Biological Biological Markers Cancer Prognosis Cancer cell line Cell Line Cells Development Diagnosis Elements Estrogen Receptors Estrogens General Transcription Factors Genetic Transcription Goals HMGN1 Protein HMGN1 gene HMGN2 gene High Mobility Group Proteins Histones Human In Vitro Individual Ions Laboratories Malignant - descriptor Malignant Neoplasms Mammary Gland Parenchyma Mass Spectrum Analysis Metabolic Methylation Mitogen-Activated Protein Kinases Molecular Nature Neoplasm Metastasis Non-Histone Chromosomal Proteins Outcome Phosphorylation Phosphorylation Site Phosphotransferases Post-Translational Protein Processing Principal Investigator Protein Kinase Proteins Role Site Solid Source Stable Isotope Labeling Staphylococcal Protein A Testing Time Tissues Transcriptional Regulation Tumor Cell Line base cancer cell cancer diagnosis casein kinase II glycosylation in vivo insight mass spectrometer outcome forecast programs research study tandem mass spectrometry tumor progression

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of this project is to understand the biological implications of the post-translational modifications of non-histone chromosomal high-mobility group (HMG) proteins. The HMG proteins are recognized as general transcription factors and they can adopt a number of post-translational modifications including phosphorylation, methylation, acetylation and glycosylation. Our hypothesis is that not only the expression, but also the post-translational modifications of HMG proteins, are correlated with cancer progression and malignant transformation. To test this hypothesis, we propose experiments according to the following specific aims: Aim 1, to examine systematically the post-translational modifications of HMG proteins in both normal and cancer cells; Aim 2, to investigate whether the level of expression and the nature of the post-translational modifications of HMG proteins are correlated with cancer progression; Aim 3, to study the phosphorylation of HMG proteins by purified protein kinase in vitro and to examine the biological implications of the post-translational modifications of HMG proteins. As studies on histone post-translational modifications have led to a wealth of new insights into the mechanisms of transcription, we anticipate that a thorough characterization of the post-translational modifications of HMG proteins will pave the way for a better understanding of the role of these non-histone chromosomal proteins on transcriptional regulation and cancer development. In addition, the outcome of proposed studies may provide important molecular biomarkers for cancer diagnosis and prognosis.

描述（由申请人提供）：该项目的长期目标是了解非组蛋白染色体高迁移率组（HMG）蛋白翻译后修饰的生物学意义。HMG蛋白是公认的通用转录因子，它们可以通过磷酸化、甲基化、乙酰化和糖基化等多种翻译后修饰。我们的假设是，HMG蛋白不仅表达，而且翻译后修饰与癌症进展和恶性转化有关。为了验证这一假设，我们根据以下具体目的提出了实验：目的1，系统地检查正常细胞和癌细胞中HMG蛋白的翻译后修饰；目的2，研究HMG蛋白的表达水平和翻译后修饰的性质是否与癌症进展相关；目的3：在体外研究纯化蛋白激酶对HMG蛋白的磷酸化作用，并研究HMG蛋白翻译后修饰的生物学意义。由于对组蛋白翻译后修饰的研究已经为转录机制带来了丰富的新见解，我们预计，对HMG蛋白翻译后修饰的全面表征将为更好地理解这些非组蛋白染色体蛋白在转录调控和癌症发展中的作用铺平道路。此外，所提出的研究结果可能为癌症诊断和预后提供重要的分子生物标志物。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Quantitative proteomic analysis reveals the perturbation of multiple cellular pathways in HL-60 cells induced by arsenite treatment.

DOI：
10.1021/pr9011359
发表时间：
2010-02-05
期刊：
JOURNAL OF PROTEOME RESEARCH
影响因子：
4.4
作者：
Xiong, Lei;Wang, Yinsheng
通讯作者：
Wang, Yinsheng

HMG modifications and nuclear function.

DOI：
10.1016/j.bbagrm.2009.11.009
发表时间：
2010-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
影响因子：
4.7
作者：
Zhang, Qingchun;Wang, Yinsheng
通讯作者：
Wang, Yinsheng

Exploring DNA-binding proteins with in vivo chemical cross-linking and mass spectrometry.

DOI：
10.1021/pr8009319
发表时间：
2009-04
期刊：
JOURNAL OF PROTEOME RESEARCH
影响因子：
4.4
作者：
Qiu, Haibo;Wang, Yinsheng
通讯作者：
Wang, Yinsheng

Coordination of PAD4 and HDAC2 in the regulation of p53-target gene expression.

DOI：
10.1038/onc.2010.51
发表时间：
2010-05-27
期刊：
ONCOGENE
影响因子：
8
作者：
Li, P.;Wang, D.;Yao, H.;Doret, P.;Hao, G.;Shen, Q.;Qiu, H.;Zhang, X.;Wang, Y.;Chen, G.;Wang, Y.
通讯作者：
Wang, Y.

Mapping Post-translational Modifications of Histones H2A, H2B and H4 in Schizosaccharomyces pombe.

绘制粟酒裂殖酵母中组蛋白 H2A、H2B 和 H4 的翻译后修饰图谱。