Related Experiment Video
Updated: Jun 13, 2026
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Altered-function p53 missense mutations identified in breast cancers can have subtle effects on transactivation
Jennifer J Jordan1, Alberto Inga, Kathleen Conway
1Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA.
Molecular Cancer Research : MCR
|April 22, 2010
Summary
Mutations in the tumor suppressor p53 impact gene regulation and cell stress responses. Functional analysis of breast cancer p53 mutants reveals diverse transactivation defects, potentially influencing clinical outcomes.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Mutations in the tumor suppressor p53 can alter its transactivation function, affecting gene activation and cellular responses to stress.
- p53 mutations are implicated in various cancers, including sporadic breast cancer and familial syndromes like Li-Fraumeni.
Purpose of the Study:
- To determine the functional fingerprints of sporadic breast cancer-associated p53 mutants.
- To assess the transactivation ability of wild-type and mutant p53 across 11 human target response elements (REs).
Main Methods:
- Utilized a cellular, isogenomic yeast model system for rapid analysis of p53 function.
- Assessed p53 transactivation at variable expression levels using qualitative and quantitative reporters.
- Analyzed 50 missense p53 mutants.
Main Results:
- 29 out of 50 missense mutants showed a loss of function.
- 21 mutants retained transactivation toward at least one RE.
- Subtle transactivation defects were revealed in some mutants at reduced expression levels, suggesting altered transcriptional activity.
Conclusions:
- Functional heterogeneity exists among p53 mutants found in breast cancer.
- Specific p53 mutation functionality may correlate with clinical parameters such as demographics, tumor appearance, and relapse rates.
- These findings suggest p53 mutation status could impact clinical behavior and treatment outcomes.
Related Concept Videos
02:23Abnormal 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...
01:12Loss 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...
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...
01:12Loss 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...
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...
01:19Interactions 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...
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...
01:05Cancer-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...
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...
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.