Related Experiment Video

Updated: Jun 11, 2025

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
09:10

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells

Published on: October 28, 2019

7.2K

Drug repositioning identifies potential autophagy inhibitors for the LIR motif p62/SQSTM1 protein

Narjes Asghari1, Ali Kian Saei1, Marco Cordani2

  • 1Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, P.O. Box 14965/161, Tehran, Iran.

Computational Biology and Chemistry
|October 6, 2024
PubMed

Insights

Researchers identified FDA-approved drugs, including kanamycin, that inhibit the p62 protein

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Drug Discovery

Background:

  • Autophagy is crucial for cellular homeostasis, but also supports tumor survival and drug resistance.
  • Sequestosome-1 (SQSTM1/p62) is a key autophagy receptor regulating selective autophagy.
  • Targeting p62's LC3-interacting region (LIR) offers a strategy to modulate autophagy.

Purpose of the Study:

  • To identify FDA-approved drugs that bind to and inhibit the LIR motif of p62.
  • To explore novel therapeutic strategies for modulating autophagy in cancer.

Main Methods:

  • Homology modeling of the p62 protein.
  • Molecular docking analysis using Molegro Virtual Docker and PyRx.
  • Toxicity profiling using ProTox-II and molecular dynamics simulations.
  • Experimental validation of drug efficacy in cancer cell lines.

Main Results:

  • Kanamycin, velpatasvir, verteporfin, and temoporfin were identified as potential inhibitors of p62 LIR binding.
  • Kanamycin demonstrated experimental inhibition of autophagy-associated acidic vesicular formation in breast cancer cells (MCF-7 and MDA-MB 231).

Conclusions:

  • FDA-approved drugs can be repurposed to target and inhibit p62's role in autophagy.
  • Kanamycin and other identified drugs show potential as novel autophagy modulators for clinical applications.
  • Further investigation is warranted to explore the therapeutic potential of these repositioned drugs.
Keywords:
AutophagyDrug repurposingLIR motifMolecular dynamicP62/SQSTM1Virtual screening

More Related Videos

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells09:51

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells

Published on: June 30, 2023

765
Study of Protein-protein Interactions in Autophagy Research14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

9.1K

Related Concept Videos

Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.2K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.2K
Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.8K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.4K
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...
3.5K