Related Experiment Video

Updated: Jul 3, 2026

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model
09:00

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model

Published on: April 17, 2026

Quercetin-induced ubiquitination and down-regulation of Her-2/neu

Jae-Hoon Jeong1, Jee Young An, Yong Tae Kwon

  • 1Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.

Journal of Cellular Biochemistry
|July 26, 2008
PubMed

Insights

Quercetin, a natural flavonoid, reduces Her-2/neu protein levels in breast cancer cells by promoting its ubiquitination and proteasomal degradation. This suggests quercetin as a potential therapeutic agent for Her-2/neu-overexpressing cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Her-2/neu (ErbB2) overexpression is linked to poor prognosis in breast cancer.
  • Quercetin is a flavonoid with studied chemopreventive properties.

Purpose of the Study:

  • To investigate the effect of quercetin on Her-2/neu protein levels and signaling pathways in breast cancer cells.
  • To elucidate the mechanism by which quercetin downregulates Her-2/neu.

Main Methods:

  • Treatment of Her-2/neu-overexpressing SK-Br3 cells with quercetin.
  • Analysis of Her-2/neu protein levels, ubiquitination, and downstream signaling (PI3K-Akt pathway).
  • Inhibition of proteasome and Hsp90 pathways to study Her-2/neu degradation.

Main Results:

  • Quercetin decreased Her-2/neu protein in a time- and dose-dependent manner.
  • Quercetin induced Her-2/neu polyubiquitination and promoted its interaction with Hsp90 and CHIP.
  • Inhibition of Hsp90 or proteasome pathways affected Her-2/neu stability and degradation.

Conclusions:

  • Quercetin downregulates Her-2/neu protein through a mechanism involving Hsp90, CHIP, and the proteasome.
  • Quercetin's ability to target Her-2/neu suggests its potential as a therapeutic strategy for relevant cancers.

More Related Videos

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations10:26

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations

Published on: November 7, 2019

Related Concept Videos

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 activation may...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...