title: BAD, a Proapoptotic Protein, Escapes ERK/RSK Phosphorylation in Deguelin and siRNA-Treated HeLa Cells.
abstract: 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.
authors.affiliation: Institute of Molecular Biology and Biotechnology and Center for Research in Molecular Medicine, the University of Lahore, Lahore, Pakistan.
authors.forename: Samra
authors.initials: S
authors.lastname: Hafeez
authors.affiliation: Institute of Molecular Biology and Biotechnology and Center for Research in Molecular Medicine, the University of Lahore, Lahore, Pakistan.
authors.forename: Mahwish
authors.initials: M
authors.lastname: Urooj
authors.affiliation: Institute of Molecular Biology and Biotechnology and Center for Research in Molecular Medicine, the University of Lahore, Lahore, Pakistan.
authors.forename: Shamiala
authors.initials: S
authors.lastname: Saleem
authors.affiliation: Institute of Molecular Biology and Biotechnology and Center for Research in Molecular Medicine, the University of Lahore, Lahore, Pakistan.
authors.forename: Zeeshan
authors.initials: Z
authors.lastname: Gillani
authors.affiliation: Institute of Molecular Biology and Biotechnology and Center for Research in Molecular Medicine, the University of Lahore, Lahore, Pakistan.
authors.forename: Sumaira
authors.initials: S
authors.lastname: Shaheen
authors.affiliation: Institute of Molecular Biology and Biotechnology and Center for Research in Molecular Medicine, the University of Lahore, Lahore, Pakistan.
authors.forename: Mahmood Husain
authors.initials: MH
authors.lastname: Qazi
authors.affiliation: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Naseer
authors.affiliation: College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, National Guards Health Affairs, Riyadh, Saudi Arabia.
authors.forename: Zafar
authors.initials: Z
authors.lastname: Iqbal
authors.affiliation: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Shakeel Ahmed
authors.initials: SA
authors.lastname: Ansari
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Absarul
authors.initials: A
authors.lastname: Haque
authors.affiliation: Department of Biotechnology, BUITEMS, Quetta, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Asif
authors.affiliation: College of Applied Medical Science, Al Majmaah University, Majmaah City, Saudi Arabia.
authors.forename: Manzoor Ahmad
authors.initials: MA
authors.lastname: Mir
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Ali
authors.affiliation: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Peter Natesan
authors.initials: PN
authors.lastname: Pushparaj
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Mohammad Sarwar
authors.initials: MS
authors.lastname: Jamal
authors.affiliation: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Rasool
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D045304:Cytochromes c / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051336:Mitochondrial Membranes / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D062105:Molecular Docking Simulation; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism; D034622:RNA Interference; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D012402:Rotenone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051025:bcl-Associated Death Protein / Q000737:chemistry / Q000378:metabolism*; D051020:bcl-X Protein / Q000737:chemistry / Q000378:metabolism
chemical_list: C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D012402:Rotenone; D045304:Cytochromes c; D019893:Ribosomal Protein S6 Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C107676:deguelin