Related Experiment Video

Updated: Jul 15, 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

WTH3 is a direct target of the p53 protein

K Tian1, Y Wang, H Xu

  • 1Department of Biochemistry and Cell Biology, State University of New York at Stony Brook, Stony Brook, NY, USA.

British Journal of Cancer
|April 12, 2007
PubMed

Insights

The WTH3 gene, regulated by p53, can reverse multidrug resistance (MDR) in cancer cells by promoting apoptosis. This discovery offers new insights into overcoming MDR development through gene regulation strategies.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Multidrug resistance (MDR) in cancer cells poses a significant challenge to chemotherapy.
  • Previous studies indicated WTH3 gene overexpression reduces MDR and restores sensitivity to anticancer drugs.
  • Differential regulation of the WTH3 gene promoter in MDR cells suggests underlying epigenetic and transcription factor involvement.

Purpose of the Study:

  • To elucidate the regulatory mechanisms governing the differential expression of the WTH3 gene.
  • To investigate the potential role of the p53 gene in regulating WTH3 expression.
  • To understand how WTH3 influences multidrug resistance and apoptosis in cancer cells.

Main Methods:

  • Identification of a p53-binding site within the WTH3 promoter region.
  • Experimental validation of p53-mediated WTH3 promoter activity using transgenes.
  • Correlation analysis of WTH3 expression and p53 gene status across various cell lines.
  • In vitro and in vivo studies to confirm direct p53 protein targeting of the WTH3 promoter.

Main Results:

  • The p53 transgene significantly upregulated the WTH3 promoter in different host cells.
  • A direct correlation was observed between WTH3 expression levels and p53 gene status.
  • The p53 protein was confirmed to directly target a specific region of the WTH3 promoter.
  • Overexpression of WTH3 induced an apoptotic phenotype in host cells.

Conclusions:

  • The WTH3 gene's negative role in MDR development is mediated through its proapoptotic function.
  • WTH3 expression is regulated at the transcriptional level by multiple mechanisms, including direct p53 gene involvement.
  • These findings highlight the p53-WTH3 axis as a potential therapeutic target for overcoming multidrug resistance in cancer.

More Related Videos

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

Purification of Ubiquitinated p53 Proteins from Mammalian Cells10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...