Related Experiment Video

Updated: Aug 7, 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

Functional analysis and molecular modeling show a preserved wild-type activity of p53(C238Y)

Marco Ferrone1, Federica Perrone, Elena Tamborini

  • 1Molecular Simulation Engineering Laboratory, Department of Chemical Engineering, University of Trieste, Piazzale Europa 1, 34127 Trieste, Italy.

Molecular Cancer Therapeutics
|July 5, 2006
PubMed

Insights

The TP53 C238Y mutation stabilizes p53 protein without inactivating its function. This specific mutation retains wild-type p53 properties, offering new insights into tumor suppressor activity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • p53 tumor suppressor is often inactivated in human cancers through mutations or MDM2 overexpression.
  • MDM2 amplification is a known mechanism for wild-type p53 inactivation, particularly in soft tissue sarcomas.
  • A novel TP53 C238Y missense mutation was previously observed in malignant peripheral nerve sheath tumors, paradoxically stabilizing p53 alongside MDM2 overexpression.

Purpose of the Study:

  • To functionally characterize the TP53 C238Y missense mutation in mammalian cells.
  • To investigate the interaction between the p53 C238Y mutant and MDM2.
  • To determine if the p53 C238Y mutant retains wild-type p53 transcriptional activity.

Main Methods:

  • MDM2 Southern blot analysis.
  • Biochemical and functional assays of p53(C238Y) and MDM2.
  • Molecular modeling of the p53 C238Y mutant.

Main Results:

  • No evidence of MDM2 gene amplification was found.
  • p53-MDM2 protein complexes were detected.
  • The p53 C238Y mutant showed phosphorylation on Ser15 and induced p21(waf1) transcription.
  • Molecular modeling indicated structural similarities between p53(C238Y) and wild-type p53.

Conclusions:

  • The TP53 C238Y mutation does not lead to MDM2 gene amplification.
  • The p53 C238Y mutant retains key functional properties of wild-type p53, including transcriptional activity.
  • This mutation represents a distinct mechanism of p53 regulation, preserving its tumor-suppressive functions.

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

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches05:56

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches

Published on: October 13, 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...
Covalently Linked Protein Regulators02:04

Covalently 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.
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
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...