Related Experiment Video

Updated: Jul 10, 2026

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene
08:18

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene

Published on: December 31, 2014

FoxO transcription factors suppress Myc-driven lymphomagenesis via direct activation of Arf

Caroline Bouchard1, Soyoung Lee, Viola Paulus-Hock

  • 1Institute of Molecular Biology and Tumor Research, 35033 Marburg, Germany.

Genes & Development
|November 3, 2007
PubMed

Insights

FoxO transcription factors are crucial for preventing lymphoma. Suppressing FoxO function accelerates lymphoma development by hindering apoptosis and regulating p19Arf expression, highlighting FoxO

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • FoxO transcription factors regulate cell cycle and stress responses.
  • Loss of FoxO function promotes Myc-driven focus formation in vitro.
  • Myc oncogene is implicated in lymphomagenesis.

Purpose of the Study:

  • To investigate the role of FoxO transcription factors in Myc-induced lymphoma development.
  • To determine if FoxO proteins regulate apoptosis and tumor suppressor genes in lymphoma.
  • To elucidate the mechanism by which Myc signaling influences FoxO activity and Arf expression.

Main Methods:

  • Stable expression of a dominant-negative FoxO moiety (dnFoxO) in Emu-myc transgenic hematopoietic stem cells.
  • Analysis of lymphoma development and apoptosis in recipient mice.
  • Assessment of p53 and p19Arf expression in lymphomas.
  • Chromatin immunoprecipitation assays to determine FoxO binding to the Ink4a/Arf locus.

Main Results:

  • dnFoxO expression in Emu-myc hematopoietic stem cells accelerated lymphoma development by reducing Myc-induced apoptosis.
  • dnFoxO expression alleviated the selective pressure for p53 allele inactivation in lymphomas.
  • p19Arf expression was undetectable in most dnFoxO-positive Myc-driven lymphomas.
  • FoxO proteins bind to the Ink4a/Arf locus and activate Arf expression.
  • Constitutive Myc signaling increased nuclear FoxO levels and enhanced FoxO binding to the Arf locus.

Conclusions:

  • FoxO transcription factors mediate Myc-induced Arf expression.
  • FoxO proteins possess tumor-suppressive capacity in the context of Myc-driven lymphomagenesis.
  • The interplay between Myc, FoxO, and Arf is critical for controlling lymphoma development.

More Related Videos

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

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

Related Concept Videos

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 daughter...
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...