Related Experiment Video

Updated: Aug 10, 2026

Inducible and Reversible Dominant-negative (DN) Protein Inhibition
08:35

Inducible and Reversible Dominant-negative (DN) Protein Inhibition

Published on: January 7, 2019

Mutant p53 proteins behave in a dominant, negative fashion in vivo

M Hachiya1, A Chumakov, C W Miller

  • 1Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine 90048.

Anticancer Research
|September 1, 1994
PubMed

Insights

Wild-type p53 and a specific His273 mutant show transcriptional activity. Other p53 mutants, including a double mutant, are inactive and inhibit wild-type p53 function, acting in a dominant-negative manner.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The p53 protein is a cellular phosphoprotein linked to cancer and cell growth control.
  • Emerging research indicates p53 also functions as a transcriptional regulator.

Purpose of the Study:

  • To investigate the transactivational properties of wild-type and mutant human p53 proteins.
  • To analyze p53 mutants at major mutational hotspots and their impact on transcriptional activity.

Main Methods:

  • Co-transfection of a p53 consensus binding sequence-controlled CAT reporter gene with wild-type or mutant p53 expression constructs.
  • Assaying transactivation activity of various p53 constructs, including single mutants, a double mutant, and a p53 variant lacking the transactivation domain.

Main Results:

  • Wild-type p53 and the His273 mutant exhibited strong transactivating activity.
  • Mutations at codons 141, 175, and 248, as well as the Tyr141/His273 double mutant, were transcriptionally inactive.
  • Inactive p53 mutants inhibited the transactivation activity of wild-type p53 and the His273 mutant in a dominant-negative manner.

Conclusions:

  • Human p53 acts as a transcriptional regulator.
  • Most p53 mutants studied are transcriptionally inactive and exert dominant-negative effects on wild-type p53.
  • The Tyr141 mutation appears dominant over the His273 mutation in a double mutant context.

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

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

Related Concept Videos

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.
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
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...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

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...
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...