Post-translational Modifications of High-mobility Group Proteins

描述(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族(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，它们可以进行许多翻译后修饰，包括磷酸化、甲基化、乙酰化和糖基化。我们的假设是，不仅HMG蛋白的表达，而且翻译后修饰，都与癌症的进展和恶变有关。为了验证这一假说，我们根据以下特定目的进行实验：目的1，系统研究HMG蛋白在正常细胞和癌细胞中的翻译后修饰；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，研究纯化的蛋白激酶体外对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。随着对组蛋白翻译后修饰的研究带来了对转录机制的大量新见解，我们预计对HMG蛋白翻译后修饰的彻底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生中的作用铺平道路。此外，拟议的研究结果可能为癌症的诊断和预后提供重要的分子生物标志物。

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.