Related Experiment Video
Updated: Jun 30, 2026
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
p53 controls hPar1 function and expression.
1Department of Oncology, Hadassah-University Medical Center, Jerusalem, Israel.
Oncogene
|September 30, 2008
Summary
The tumor suppressor p53 directly binds to and regulates the expression of human protease-activated receptor 1 (hPar1). This interaction impacts cancer progression by modulating hPar1 function, identifying hPar1 as a p53 target gene.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Human protease-activated receptor 1 (hPar1) is a receptor for thrombin with a role in tumor progression.
- Inactivation of the tumor suppressor gene p53 is common in cancer.
Purpose of the Study:
- To investigate the relationship between p53 and hPar1 in cancer.
- To determine if p53 directly regulates hPar1 expression and function.
Main Methods:
- Bioinformatic analysis of the hPar1 promoter for p53 binding sites.
- Reporter assays using temperature-sensitive p53 and p53 mutants.
- Chromatin immunoprecipitation (ChIP) to confirm p53-hPar1 interaction.
- Functional assays including pFAK levels and Matrigel invasion assays.
Main Results:
- An inverse correlation between wild-type p53 and hPar1 expression, and a direct correlation with mutant p53.
- p53 binds to hPar1 chromatin, directly affecting its promoter activity.
- p53 attenuates hPar1 function, evidenced by reduced pFAK and invasion.
- Restoring hPar1 expression rescued p53-mediated inhibition.
Conclusions:
- hPar1 is a direct transcriptional target of p53.
- p53 directly binds to hPar1 chromatin, regulating its expression and function.
- This interaction has implications for understanding cancer progression and therapeutic strategies.
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...
01:23Negative 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.
02:36DNA 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...
02:36DNA 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...
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...
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.