A peptide fragment of azurin induces a p53-mediated cell cycle arrest in human breast cancer cells
| Autor: | Fatima Lekmine, Craig W. Beattie, Tohru Yamada, Dibyen Majumdar, Marissa L. King, Rajeshwari R. Mehta, Tapas K. Das Gupta, Albert Green, Anne Shilkaitis, Konstantin Christov, Laura Bratescu |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Proteasome Endopeptidase Complex
Cancer Research Cell cycle checkpoint Cyclin A Breast Neoplasms Cell Cycle Proteins Mice Azurin Cell Line Tumor Cyclins medicine Animals Humans Cytotoxic T cell Cell Proliferation chemistry.chemical_classification biology Protein Stability Kinase Cell Cycle Cancer medicine.disease Xenograft Model Antitumor Assays Peptide Fragments Amino acid Cell biology Bromodeoxyuridine Oncology chemistry Apoptosis Cancer cell biology.protein Female Tumor Suppressor Protein p53 Protein Processing Post-Translational Protein Binding |
| Zdroj: | Molecular Cancer Therapeutics. 8:2947-2958 |
| ISSN: | 1538-8514 1535-7163 |
| DOI: | 10.1158/1535-7163.mct-09-0444 |
| Popis: | We report that amino acids 50 to 77 of azurin (p28) preferentially enter the human breast cancer cell lines MCF-7, ZR-75-1, and T47D through a caveolin-mediated pathway. Although p28 enters p53 wild-type MCF-7 and the isogenic p53 dominant-negative MDD2 breast cancer cell lines, p28 only induces a G2-M-phase cell cycle arrest and apoptosis in MCF-7 cells. p28 exerts its antiproliferative activity by reducing proteasomal degradation of p53 through formation of a p28:p53 complex within a hydrophobic DNA-binding domain (amino acids 80-276), increasing p53 levels and DNA-binding activity. Subsequent elevation of the cyclin-dependent kinase inhibitors p21 and p27 reduces cyclin-dependent kinase 2 and cyclin A levels in a time-dependent manner in MCF-7 cells but not in MDD2 cells. These results suggest that p28 and similar peptides that significantly reduce proteasomal degradation of p53 by a MDM2-independent pathway(s) may provide a unique series of cytostatic and cytotoxic (apoptotic) chemotherapeutic agents. [Mol Cancer Ther 2009;8(10):2947–58] |
| Databáze: | OpenAIRE |
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