Proteomic analysis and abrogated expression ofO-GlcNAcylated proteins associated with primary breast cancer
| Autor: | Parunya Chaiyawat, Daranee Chokchaichamnankit, Ratana Charoenwattanasatien, Voraratt Champattanachai, Jisnuson Svasti, Chantragan Srisomsap, Thanong Phueaouan, Pukkavadee Netsirisawan, Phaibul Punyarit |
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| Rok vydání: | 2013 |
| Předmět: |
Proteome
Immunoblotting Breast Neoplasms Biology N-Acetylglucosaminyltransferases Heterogeneous ribonucleoprotein particle Models Biological Biochemistry Heterogeneous-Nuclear Ribonucleoproteins Acetylglucosamine Breast cancer Gene expression Biomarkers Tumor medicine Humans Electrophoresis Gel Two-Dimensional Lactic Acid Molecular Biology Glycoproteins chemistry.chemical_classification Gene knockdown Reproducibility of Results Cancer medicine.disease Warburg effect chemistry Cancer research Female Glycoprotein |
| Zdroj: | PROTEOMICS. 13:2088-2099 |
| ISSN: | 1615-9853 |
| DOI: | 10.1002/pmic.201200126 |
| Popis: | O-GlcNAcylation is a dynamic PTM of nuclear and cytoplasmic proteins, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase, which catalyze the addition and removal of O-GlcNAc, respectively. This modification is associated with glucose metabolism, which plays important roles in many diseases including cancer. Although emerging evidence reveals that some tumor-associated proteins are O-GlcNAc modified, the total O-GlcNAcylation in cancer is still largely unexplored. Here, we demonstrate that O-GlcNAcylation was increased in primary breast malignant tumors, not in benign tumors and that this augmentation was associated with increased expression of OGT level. Using 2D O-GlcNAc immnoblotting and LC-MS/MS analysis, we successfully identified 29 proteins, with seven being uniquely O-GlcNAcylated or associated with O-GlcNAcylation in cancer. Of these identified proteins, some were related to the Warburg effect, including metabolic enzymes, proteins involved in stress responses and biosynthesis. In addition, proteins associated with RNA metabolism, gene expression, and cytoskeleton were highly O-GlcNAcylated or associated with O-GlcNAcylation. Moreover, OGT knockdown showed that decreasing O-GlcNAcylation was related to inhibition of the anchorage-independent growth in vitro. These data indicate that aberrant protein O-GlcNAcylation is associated with breast cancer. Abnormal modification of these O-GlcNAc-modified proteins might be one of the vital malignant characteristics of cancer. |
| Databáze: | OpenAIRE |
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