Related Experiment Video

Updated: Apr 16, 2026

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH
07:54

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH

Published on: August 19, 2014

17.7K

p14(ARF) Prevents Proliferation of Aneuploid Cells by Inducing p53-Dependent Apoptosis

Lorena Veneziano1, Viviana Barra1, Laura Lentini1

  • 1Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo, Italy.

Journal of Cellular Physiology
|March 11, 2015
PubMed

Insights

The tumor suppressor p14(ARF) counteracts aneuploid cell proliferation by activating p53-dependent apoptosis, reducing chromosome instability and aberrant mitoses in cancer cells.

Area of Science:

  • Cell Biology
  • Cancer Biology
  • Genetics

Background:

  • Reduced Spindle Assembly Checkpoint (SAC) function leads to chromosome instability and aneuploidy, common in cancer.
  • The tumor suppressor p14(ARF) stabilizes p53, halting cell progression in response to oncogenic stress.
  • Previous findings suggest p14(ARF) deficiency contributes to aneuploid cell maintenance.

Purpose of the Study:

  • To investigate the role of p14(ARF) in controlling the proliferation of aneuploid cells.
  • To determine if p14(ARF) re-expression can reduce aneuploidy and associated mitotic defects.

Main Methods:

  • Ectopic expression of p14(ARF) in HCT116 cells with silenced MAD2 (a SAC component) to induce aneuploidy.
  • Quantification of aneuploid cells and aberrant mitoses.
  • Assessment of apoptosis and p53 protein levels, including in p53 knockout cells.

Main Results:

  • p14(ARF) re-expression decreased the number of aneuploid cells and aberrant mitoses in MAD2-silenced cells.
  • Ectopic p14(ARF) induced apoptosis in MAD2-depleted cells, correlating with increased p53 levels.
  • Apoptosis induction by p14(ARF) was dependent on p53, as it was not observed in p53 knockout cells.

Conclusions:

  • The tumor suppressor p14(ARF) plays a role in eliminating aneuploid cells.
  • p14(ARF) promotes p53-dependent apoptosis in aneuploid cells, thereby counteracting their proliferation.
  • These findings highlight a potential therapeutic strategy targeting p14(ARF) in cancers with aneuploidy.

More Related Videos

Generation and Isolation of Cell Cycle-arrested Cells with Complex Karyotypes05:22

Generation and Isolation of Cell Cycle-arrested Cells with Complex Karyotypes

Published on: April 13, 2018

11.2K
Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

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

Published on: August 4, 2019

10.2K

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...
5.5K
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.
39.2K
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
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
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.6K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.3K