Related Experiment Video

Updated: Jul 3, 2026

In Situ Monitoring of Transiently Formed Molecular Chaperone Assemblies in Bacteria, Yeast, and Human Cells
08:58

In Situ Monitoring of Transiently Formed Molecular Chaperone Assemblies in Bacteria, Yeast, and Human Cells

Published on: September 2, 2019

Efrapeptin J, a new down-regulator of the molecular chaperone GRP78 from a marine Tolypocladium sp

Yoichi Hayakawa1, Yuki Hattori, Takashi Kawasaki

  • 1Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan. hykw@rs.noda.tus.ac.jp

The Journal of Antibiotics
|August 1, 2008
PubMed

Insights

A novel marine peptide, efrapeptin J, effectively down-regulates glucose-regulated protein 78 (GRP78) and induces cancer cell death. This discovery offers potential new avenues for cancer therapy development.

Area of Science:

  • Marine natural products chemistry
  • Molecular biology
  • Cancer research

Background:

  • Glucose-regulated protein 78 (GRP78) is a key molecular chaperone implicated in cancer cell survival and drug resistance.
  • Identifying novel regulators of GRP78 is crucial for developing new anti-cancer strategies.

Purpose of the Study:

  • To isolate and characterize novel compounds from marine fungi with potential anti-cancer activity.
  • To investigate the effect of efrapeptin J on GRP78 expression and its impact on cancer cell viability.

Main Methods:

  • Isolation and structural elucidation of efrapeptin J from Tolypocladium sp. AMB18 using high-resolution FAB-MS and NMR spectroscopy.
  • Assessing the inhibitory effects of efrapeptins on GRP78 promoter activity using luciferase reporter assays in HT1080 fibrosarcoma cells.
  • Evaluating the impact of efrapeptin J on GRP78 protein levels and cell death induction in HT1080 and MKN-74 gastric cancer cells.

Main Results:

  • Efrapeptin J, a linear pentadecapeptide, was isolated and its structure determined.
  • Efrapeptins F, G, and J demonstrated dose-dependent inhibition of GRP78 promoter activity.
  • Efrapeptin J significantly reduced GRP78 protein expression and induced cell death in cancer cells, particularly under endoplasmic reticulum stress.

Conclusions:

  • Efrapeptin J is a potent down-regulator of GRP78 with significant anti-cancer properties.
  • The marine-derived peptide efrapeptin J represents a promising lead compound for the development of novel cancer therapeutics targeting GRP78.
  • Further research into efrapeptin J's mechanism of action and in vivo efficacy is warranted.

More Related Videos

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep105011:27

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050

Published on: May 13, 2020

Studies of Chaperone-Cochaperone Interactions using Homogenous Bead-Based Assay06:51

Studies of Chaperone-Cochaperone Interactions using Homogenous Bead-Based Assay

Published on: July 21, 2021

Related Concept Videos

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...
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...
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...
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...