BAD, a Proapoptotic Protein, Escapes ERK/RSK Phosphorylation in Deguelin and siRNA-Treated HeLa Cells
| Autor: | Manzoor Ahmad Mir, Mahmood Husain Qazi, Ashraf Ali, Mahwish Urooj, Peter Natesan Pushparaj, Shakeel Ahmed Ansari, Sumaira Shaheen, Mahmood Rasool, Zeeshan Gillani, Samra Hafeez, Zafar Iqbal, Shamiala Saleem, Muhammad Imran Naseer, Mohammad Sarwar Jamal, Absarul Haque, Muhammad Asif |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Small interfering RNA bcl-X Protein lcsh:Medicine Apoptosis Biology HeLa 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Rotenone Humans Gene silencing Phosphorylation lcsh:Science Mitogen-Activated Protein Kinase 1 Binding Sites Mitogen-Activated Protein Kinase 3 Multidisciplinary Ribosomal Protein S6 Kinases lcsh:R Cytochromes c Transfection biology.organism_classification Protein Structure Tertiary Cell biology Molecular Docking Simulation 030104 developmental biology Proto-Oncogene Proteins c-bcl-2 chemistry 030220 oncology & carcinogenesis Mitochondrial Membranes Myeloid Cell Leukemia Sequence 1 Protein RNA Interference bcl-Associated Death Protein lcsh:Q Deguelin HeLa Cells Protein Binding Research Article |
| Zdroj: | PLoS ONE, Vol 11, Iss 1, p e0145780 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | This study has been undertaken to explore the therapeutic effects of deguelin and specific siRNAs in HeLa cells. The data provided clearly show the silencing of ERK 1/2 with siRNAs and inhibition of ERK1/2 with deguelin treatment in HeLa cells. Additionally, we are providing information that deguelin binds directly to anti-apoptotic Bcl-2, Bcl-xl and Mcl-1 in the hydrophobic grooves, thereby releasing BAD and BAX from dimerization with these proteins. This results in increased apoptotic activity through the intrinsic pathway involved in rupture of mitochondrial membrane and release of cytochrome C. Evidence for inhibition of ERK1/2 by deguelin and escape of BAD phosphorylation at serine 112 through ERK/RSK pathway has been further fortified by obtaining similar results by silencing ERK 1/2 each with specific siRNAs. Increase in BAD after treatment with deguelin or siRNAs has been interpreted to mean that deguelin acts through several alternative pathways and therefore can be used as effective therapeutic agent. |
| Databáze: | OpenAIRE |
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