Related Experiment Video

Updated: Apr 13, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

10.2K

Transcription-independent ARF regulation in oncogenic stress-mediated p53 responses

Delin Chen1, Jing Shan, Wei-Guo Zhu

  • 1Institute for Cancer Genetics, and Department of Pathology and Cell Biology College of Physicians & Surgeons, Columbia University, 1130 St Nicholas Avenue, New York, New York 10032, USA.

Nature
|March 9, 2010
PubMed

Insights

Tumor suppressor ARF is unstable in normal cells but stabilized in cancer. A newly identified ubiquitin ligase, ULF, targets ARF for degradation, revealing a dynamic ARF-p53 pathway critical for tumor suppression.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cellular Regulation

Background:

  • The ARF-p53 pathway is crucial for tumor suppression, particularly under oncogenic stress.
  • Previous assumptions suggested ARF stability and slow transcriptional induction, contrasting with faster DNA damage-induced p53 activation.
  • The ARF-p53 axis's role in tumor suppression is more fundamental than previously understood.

Purpose of the Study:

  • To investigate the regulation of ARF stability and its role in the ARF-p53 pathway.
  • To identify factors controlling ARF degradation and stabilization in normal and cancerous cells.
  • To elucidate transcription-independent mechanisms in ARF regulation.

Main Methods:

  • Biochemical purification to identify ARF-interacting proteins.
  • In vitro and in vivo interaction studies between ARF and identified ligase.
  • Ubiquitylation and degradation assays.
  • Knockdown studies of the identified ubiquitin ligase.
  • Analysis of ARF stabilization in cancer cells with overexpressed NPM and c-Myc.

Main Results:

  • ARF is unstable in normal human cells but stabilized in cancerous cells.
  • A specific ubiquitin ligase, ULF, was identified that targets ARF for ubiquitylation and degradation.
  • ULF knockdown stabilizes ARF in normal cells, leading to p53-mediated growth arrest.
  • Overexpressed NPM and c-Myc abrogate ULF-mediated ARF ubiquitylation, promoting ARF stabilization in cancer.

Conclusions:

  • ARF regulation is dynamic and involves rapid degradation in normal cells, which is impaired in cancer.
  • The ubiquitin ligase ULF is a key regulator of ARF stability.
  • Transcription-independent mechanisms, influenced by NPM and c-Myc, are critical for ARF regulation in oncogenic stress response.

More Related Videos

Measurements of Physiological Stress Responses in C. Elegans10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

15.3K
Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

341

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
39.1K
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...
10.4K
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...
5.4K
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...
5.1K
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...
3.2K
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...
3.4K