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Related Concept Videos

Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
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Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Treatment Resistent Cancers02:56

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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
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Abnormal Proliferation02:23

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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 daughter...

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Related Experiment Video

Updated: Jul 4, 2026

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
11:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

IRF4 addiction in multiple myeloma.

Arthur L Shaffer1, N C Tolga Emre, Laurence Lamy

  • 1Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Nature
|June 24, 2008
PubMed
Summary

Inhibition of interferon regulatory factor 4 (IRF4) is toxic to multiple myeloma cells, revealing a shared vulnerability across subtypes. This study uncovers a critical IRF4-MYC autoregulatory circuit driving myeloma progression.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • Interferon regulatory factor 4 (IRF4) is crucial for lymphocyte activation and plasma cell development.
  • Multiple myeloma is a plasma cell malignancy with complex molecular heterogeneity and therapies that are not curative.
  • Targeting shared molecular pathways across myeloma subtypes is essential for developing new therapeutic strategies.

Purpose of the Study:

  • To identify novel therapeutic targets in multiple myeloma by screening for genes whose inhibition is toxic to myeloma cells.
  • To elucidate the molecular mechanisms underlying IRF4's role in myeloma, including its target genes and regulatory networks.
  • To investigate the potential of targeting the IRF4 network as a pan-myeloma therapeutic strategy.

Main Methods:

  • Loss-of-function RNA interference-based genetic screen to identify essential genes in myeloma cell lines.
  • Gene expression profiling to analyze global gene expression changes.
  • Genome-wide chromatin immunoprecipitation (ChIP) analysis to identify direct IRF4 target genes.

Main Results:

  • IRF4 inhibition demonstrated toxicity across diverse multiple myeloma cell lines, irrespective of their specific oncogenic drivers.
  • An extensive network of IRF4 target genes was identified, including MYC, which is directly regulated by IRF4 in B cells and myeloma.
  • A reciprocal autoregulatory circuit was discovered where MYC directly transactivates IRF4 in myeloma cells.
  • Myeloma cells exhibit addiction to an aberrant IRF4 regulatory network that integrates normal plasma cell and activated B cell gene expression programs.

Conclusions:

  • IRF4 is a critical vulnerability in multiple myeloma, offering a potential therapeutic target applicable to all subtypes.
  • The identified IRF4-MYC autoregulatory loop represents a key oncogenic mechanism driving myeloma pathogenesis.
  • Targeting this aberrant IRF4 regulatory network holds promise for novel, broadly effective multiple myeloma therapies.