Related Experiment Video

Updated: Aug 23, 2026

Aip1p Dynamics Are Altered by the R256H Mutation in Actin
08:57

Aip1p Dynamics Are Altered by the R256H Mutation in Actin

Published on: July 30, 2014

Myc-ARF (alternate reading frame) interaction inhibits the functions of Myc

Abhishek Datta1, Alo Nag, Wei Pan

  • 1Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 900 S. Ashland Avenue, Chicago, IL 60607, USA.

The Journal of Biological Chemistry
|June 17, 2004
PubMed

Insights

The alternate reading frame (ARF) tumor suppressor protein targets c-Myc, inhibiting its function and cell cycle progression. This ARF activity occurs independently of the ARF-p53 pathway, revealing a novel mechanism for cell cycle regulation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Cycle Regulation

Background:

  • The tumor suppressor protein ARF (alternate reading frame) is known to inhibit MDM2, stabilizing and activating p53.
  • ARF's role in cell cycle regulation is primarily understood through its interaction with the ARF-p53 pathway.

Purpose of the Study:

  • To investigate potential p53-independent functions of ARF in cell cycle regulation.
  • To determine if ARF interacts with and regulates other key cellular proteins involved in cell cycle progression.

Main Methods:

  • Co-immunoprecipitation assays to assess protein interactions.
  • Immunofluorescence microscopy to determine protein localization.
  • Analysis of gene expression and cell cycle progression in inducible cell lines with varying p53 status.

Main Results:

  • ARF directly interacts with c-Myc independently of MDM2 or p53.
  • ARF binding causes c-Myc relocalization from the nucleoplasm to the nucleolus.
  • ARF inhibits c-Myc-driven transcription and S-phase entry, even in cells lacking functional p53.

Conclusions:

  • c-Myc is a direct target of ARF, and ARF attenuates c-Myc activity independently of the ARF-p53 axis.
  • ARF possesses a p53-independent mechanism to inhibit cell cycle progression by targeting c-Myc.

More Related Videos

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

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...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
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...