Related Experiment Video

Updated: Apr 17, 2026

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
04:56

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

Published on: December 30, 2025

346

Gain of function mutant p53 proteins cooperate with E2F4 to transcriptionally downregulate RAD17 and BRCA1 gene

Fabio Valenti1, Federica Ganci1, Giulia Fontemaggi1

  • 1Translational Oncogenomic Unit, Molecular Medicine Area, Regina Elena National Cancer Institute, Rome 00144, Italy.

Oncotarget
|February 5, 2015
PubMed

Insights

Gain-of-function mutant p53 proteins impair DNA repair by inhibiting BRCA1 and RAD17 expression, leading to genomic instability in cancer. This contributes to reduced survival in TP53-mutated cancer patients.

Area of Science:

  • Molecular Biology
  • Cancer Genetics
  • Genomics

Background:

  • Genomic instability is a hallmark of human cancers.
  • TP53 gene mutations occur in about half of all human cancers.
  • Mutant p53 proteins can acquire gain-of-function activities.

Purpose of the Study:

  • To investigate the role of gain-of-function mutant p53 in regulating DNA repair genes.
  • To determine the impact of mutant p53 on BRCA1 and RAD17 expression.
  • To explore the clinical relevance of these findings in cancer patients.

Main Methods:

  • Analysis of gene expression in cancer cells and patient cohorts.
  • Investigation of transcriptional regulation by mutant p53.
  • Correlation of DNA repair gene expression with patient survival data.

Main Results:

  • Gain-of-function mutant p53 proteins transcriptionally repress BRCA1 and RAD17 expression.
  • Mutant p53/E2F4 complex binding to BRCA1 and RAD17 promoters inhibits their expression.
  • Reduced BRCA1 and RAD17 mRNA levels are observed in TP53-mutated HNSCC patients.
  • Low DNA repair gene expression correlates with reduced relapse-free survival in TP53-mutated breast cancer patients.

Conclusions:

  • Transcriptionally active gain-of-function mutant p53 proteins contribute to genomic instability.
  • Impairment of DNA repair mechanisms by mutant p53 is a key factor.
  • These findings reveal a novel mechanism linking mutant p53 to cancer progression and patient outcome.
Keywords:
BRCA1DNA damage responseRAD17gain-of-functiongenomic instabilitymutant p53

More Related Videos

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
Analysis of Cell Cycle Position in Mammalian Cells12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

61.7K

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...
10.4K
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...
3.4K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
8.0K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
12.2K