p16(Ink4a) interferes with Abelson virus transformation by enhancing apoptosis

Related Experiment Video

Updated: Aug 15, 2026

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death
13:54

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death

Published on: October 21, 2012

Zohar Sachs1, Norman E Sharpless, Ronald A DePinho

  • 1Department of Pathology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

Journal of Virology
|March 16, 2004
PubMed

Insights

Abelson virus (Ab-MLV) transformation involves crisis, often bypassed by inactivating the p53 pathway. This study shows both p19Arf and p16Ink4a tumor suppressors influence Ab-MLV transformation, with p16Ink4a inducing apoptosis.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Abelson virus (Ab-MLV) transformation of pre-B cells is a multistep process.
  • Crisis, a period of erratic growth and apoptosis, is a hallmark of this transformation.
  • Inactivation of the p53 tumor suppressor pathway, via p53 mutation or p19Arf downregulation, is crucial for transformation.

Purpose of the Study:

  • To investigate the role of the Ink4a/Arf locus, encoding both p19Arf and p16Ink4a tumor suppressors, in Ab-MLV transformation.
  • To determine if p16Ink4a influences Ab-MLV transformation independently of p19Arf.

Main Methods:

  • Comparison of primary Ab-MLV transformants from Arf(-/-) and p16Ink4a(-/-) mice.
  • Analysis of Ink4a/Arf(-/-) cells infected with a virus expressing v-Abl and p16Ink4a.
  • Assessment of cell cycle profiles and apoptosis levels.

Main Results:

  • While Arf(-/-) cells showed some crisis, p16Ink4a(-/-) transformants consistently experienced crisis but established more readily than wild-type cells.
  • p16Ink4a expression in Ink4a/Arf(-/-) cells did not alter cell cycle profiles.
  • p16Ink4a expression significantly increased apoptosis in primary transformants.

Conclusions:

  • Both p19Arf and p16Ink4a products of the Ink4a/Arf locus are important in Ab-MLV transformation.
  • p16Ink4a suppresses transformation not only by cell cycle inhibition but also by inducing apoptosis.

More Related Videos

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses10:13

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses

Published on: May 6, 2019

In Vitro Establishment of a Genetically Engineered Murine Head and Neck Cancer Cell Line using an Adeno-Associated Virus-Cas9 System05:45

In Vitro Establishment of a Genetically Engineered Murine Head and Neck Cancer Cell Line using an Adeno-Associated Virus-Cas9 System

Published on: January 9, 2020

Related Concept Videos

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...
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...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
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...
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...