Identification of ALDH4 as a p53-inducible gene and its protective role in cellular stresses

Related Experiment Video

Updated: Aug 26, 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

Kyong-Ah Yoon1, Yusuke Nakamura1, Hirofumi Arakawa2,3

  • 1Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

Journal of Human Genetics
|February 27, 2004
PubMed

Insights

The tumor suppressor p53 directly activates ALDH4 gene expression, which helps cancer cells resist damage from reactive oxygen species (ROS). This finding reveals a new protective mechanism mediated by p53.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • The tumor suppressor protein p53 is a critical regulator of cellular responses to stress.
  • Identifying novel p53 targets is crucial for understanding its multifaceted roles in cancer.

Purpose of the Study:

  • To identify new genes directly regulated by p53.
  • To investigate the role of aldehyde dehydrogenase 4 (ALDH4) in p53-mediated cellular protection.

Main Methods:

  • cDNA microarray analysis to screen for p53-regulated genes.
  • Electrophoretic mobility shift assay (EMSA) and ChIP assays to confirm p53 binding.
  • Reporter assays to assess transcriptional activity.
  • Antisense oligonucleotide inhibition and cell viability assays.

Main Results:

  • Aldehyde dehydrogenase 4 (ALDH4) was identified as a direct transcriptional target of p53.
  • ALDH4 expression is induced by DNA damage in a p53-dependent manner.
  • Overexpression of ALDH4 confers resistance to reactive oxygen species (ROS)-induced cell damage.

Conclusions:

  • p53 directly activates ALDH4 transcription, contributing to cellular defense against ROS.
  • ALDH4 may play a significant role in the protective functions of p53 against oxidative stress and cell death.

More Related Videos

Application of AlDeSense to Stratify Ovarian Cancer Cells Based on Aldehyde Dehydrogenase 1A1 Activity09:59

Application of AlDeSense to Stratify Ovarian Cancer Cells Based on Aldehyde Dehydrogenase 1A1 Activity

Published on: March 31, 2023

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...
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.
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...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...