Related Experiment Video

Updated: Sep 13, 2025

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization
08:57

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization

Published on: October 6, 2019

10.1K

LAMP5 modulates IRF4 stability and nuclear transport: a critical mechanism in myeloma progression and therapy

Zou Li1, Rui Liu1, Zhihong Fang2,3

  • 1Cancer Research Center, School of Medicine, Shenzhen Research Institute of Xiamen University, Xiamen University, Xiamen, Fujian, China.

Oncogene
|July 28, 2025
PubMed

Insights

Lysosomal-associated membrane protein 5 (LAMP5) stabilizes Interferon regulatory factor 4 (IRF4) in multiple myeloma, promoting cancer growth. Pyrazofurin disrupts this interaction, offering a potential new treatment for this blood cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Hematology

Background:

  • Multiple myeloma pathogenesis involves unclear molecular mechanisms and limited targeted therapies.
  • Interferon regulatory factor 4 (IRF4) is crucial in myeloma progression, but its protein homeostasis is poorly understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms regulating IRF4 protein homeostasis in multiple myeloma.
  • To identify novel therapeutic targets and strategies for multiple myeloma treatment.

Main Methods:

  • Investigated the interaction between lysosomal-associated membrane protein 5 (LAMP5) and IRF4.
  • Utilized techniques to assess protein degradation pathways (autophagy-lysosome).
  • Examined nuclear transport mechanisms involving karyopherin α2 (KPNA2).
  • Performed high-throughput drug screening to identify inhibitors of the LAMP5-IRF4 interaction.

Main Results:

  • LAMP5 interacts with IRF4, inhibiting its autophagy-lysosome degradation and promoting myeloma progression.
  • LAMP5 enhances IRF4 nuclear transport via KPNA2, preventing cytoplasmic degradation.
  • A positive feedback loop between nuclear IRF4 and c-MYC activates LAMP5 transcription, driving myeloma.
  • Pyrazofurin was identified as an inhibitor disrupting the LAMP5-IRF4 interaction, leading to IRF4 degradation and myeloma inhibition.

Conclusions:

  • LAMP5 plays a critical role in maintaining IRF4 stability and promoting multiple myeloma.
  • The identified IRF4-LAMP5-c-MYC regulatory loop is a key driver of myeloma progression.
  • Pyrazofurin represents a promising therapeutic agent targeting the LAMP5-IRF4 interaction for myeloma treatment.

More Related Videos

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice08:09

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice

Published on: March 24, 2017

8.2K
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

272

Related Concept Videos

Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.9K
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...
2.6K