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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA116522-03S2
Application #
7882769
Study Section
Enabling Bioanalytical and Biophysical Technologies Study Section (EBT)
Program Officer
Ogunbiyi, Peter
Project Start
2007-08-01
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2011-07-31
Support Year
3
Fiscal Year
2009
Total Cost
$57,263
Indirect Cost
Name
University of California Riverside
Department
Chemistry
Type
Schools of Earth Sciences/Natur
DUNS #
627797426
City
Riverside
State
CA
Country
United States
Zip Code
92521
Xiong, Lei; Wang, Yinsheng (2011) Mapping Post-translational Modifications of Histones H2A, H2B and H4 in Schizosaccharomyces pombe. Int J Mass Spectrom 301:159-165
Li, P; Wang, D; Yao, H et al. (2010) Coordination of PAD4 and HDAC2 in the regulation of p53-target gene expression. Oncogene 29:3153-62
Xiong, Lei; Zhang, Jing; Yuan, Bifeng et al. (2010) Global proteome quantification for discovering imatinib-induced perturbation of multiple biological pathways in K562 human chronic myeloid leukemia cells. J Proteome Res 9:6007-15
Dong, Xiaoli; Xiong, Lei; Jiang, Xinning et al. (2010) Quantitative proteomic analysis reveals the perturbation of multiple cellular pathways in jurkat-T cells induced by doxorubicin. J Proteome Res 9:5943-51
Xiong, Lei; Adhvaryu, Keyur K; Selker, Eric U et al. (2010) Mapping of lysine methylation and acetylation in core histones of Neurospora crassa. Biochemistry 49:5236-43
Dong, Xiaoli; Cheng, Jinsheng; Li, Jinghong et al. (2010) Graphene as a novel matrix for the analysis of small molecules by MALDI-TOF MS. Anal Chem 82:6208-14
Zhang, Qingchun; Wang, Yinsheng (2010) HMG modifications and nuclear function. Biochim Biophys Acta 1799:28-36
Xiong, Lei; Wang, Yinsheng (2010) Quantitative proteomic analysis reveals the perturbation of multiple cellular pathways in HL-60 cells induced by arsenite treatment. J Proteome Res 9:1129-37
Qiu, Haibo; Wang, Yinsheng (2009) Exploring DNA-binding Proteins with In Vivo Chemical Cross-linking and Mass Spectrometry. J Proteome Res :
Jiang, Dianlu; Li, Xiangjun; Williams, Renee et al. (2009) Ternary complexes of iron, amyloid-beta, and nitrilotriacetic acid: binding affinities, redox properties, and relevance to iron-induced oxidative stress in Alzheimer's disease. Biochemistry 48:7939-47

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