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. ? ? ?
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