Related Experiment Video

Updated: Mar 27, 2026

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
10:50

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Published on: April 24, 2021

1.4K

BAD, a Proapoptotic Protein, Escapes ERK/RSK Phosphorylation in Deguelin and siRNA-Treated HeLa Cells

Samra Hafeez1, Mahwish Urooj1, Shamiala Saleem1

  • 1Institute of Molecular Biology and Biotechnology and Center for Research in Molecular Medicine, the University of Lahore, Lahore, Pakistan.

Plos One
|January 9, 2016
PubMed

Insights

Deguelin effectively inhibits ERK1/2 and promotes apoptosis in HeLa cells by disrupting anti-apoptotic proteins. This suggests deguelin

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The intrinsic apoptotic pathway is crucial for cell death.
  • Dysregulation of apoptosis is implicated in cancer development.
  • Targeting key regulatory proteins offers therapeutic potential.

Purpose of the Study:

  • To investigate the therapeutic effects of deguelin and specific siRNAs in HeLa cells.
  • To elucidate the molecular mechanisms underlying deguelin's action.
  • To evaluate deguelin as a potential anti-cancer agent.

Main Methods:

  • Utilized specific small interfering RNAs (siRNAs) for gene silencing.
  • Administered deguelin to HeLa cells for treatment.
  • Analyzed protein interactions and apoptotic markers.

Main Results:

  • Deguelin and siRNAs effectively inhibited Extracellular signal-Regulated Kinase 1/2 (ERK1/2) in HeLa cells.
  • Deguelin directly binds to anti-apoptotic proteins (Bcl-2, Bcl-xl, Mcl-1), releasing pro-apoptotic proteins (BAD, BAX).
  • This interaction triggers the intrinsic apoptotic pathway, leading to mitochondrial membrane rupture and cytochrome C release.

Conclusions:

  • Deguelin induces apoptosis through direct interaction with anti-apoptotic proteins and inhibition of the ERK1/2 pathway.
  • Deguelin's multifaceted mechanism suggests its potential as an effective therapeutic agent.
  • Further research into deguelin's alternative pathways is warranted.

More Related Videos

Monitoring On-Target Signaling Responses in Larval Zebrafish - Z-REX Unmasks Precise Mechanisms of Electrophilic Drugs and Metabolites05:28

Monitoring On-Target Signaling Responses in Larval Zebrafish - Z-REX Unmasks Precise Mechanisms of Electrophilic Drugs and Metabolites

Published on: June 2, 2023

1.5K
Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

9.2K

Related Concept Videos

Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
5.5K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.2K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
3.0K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.3K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.9K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.9K