Related Experiment Video

Updated: Aug 10, 2026

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method
09:32

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method

Published on: September 10, 2017

Phosphorylation of murine p53 at ser-18 regulates the p53 responses to DNA damage

C Chao1, S Saito, C W Anderson

  • 1Division of Biology and Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 18, 2000
PubMed

Insights

Phosphorylation of mouse p53 at Ser-18 is crucial for the full p53-mediated DNA damage response to radiation and UV light. However, it is not essential for ATM-dependent cellular resistance or C-terminal acetylation after DNA damage.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • Serine 15 (Ser-15) of human p53, equivalent to Serine 18 (Ser-18) in mouse p53, is a key phosphorylation site targeted by ataxia-telangiectasia mutated (ATM) family kinases.
  • This phosphorylation event is triggered by DNA-damaging agents such as ionizing radiation (IR) and UV light, playing a critical role in the cellular response to genotoxic stress.

Purpose of the Study:

  • To investigate the specific role of endogenous murine p53 phosphorylation at Ser-18 in biological responses to DNA damage.
  • To determine whether Ser-18 phosphorylation is essential for ATM-dependent cellular resistance and p53 C-terminal acetylation following DNA damage.

Main Methods:

  • Utilized homologous recombination in mouse embryonic stem (ES) cells to introduce a Ser-18 to Alanine (Ala) missense mutation in both alleles of the endogenous p53 gene.
  • Analyzed the impact of this mutation on p53-mediated responses, ATM-dependent cellular resistance, and C-terminal acetylation after exposure to IR and UV radiation.

Main Results:

  • Phosphorylation of murine p53 at Ser-18 was found to be essential for a complete p53-mediated response to IR and UV radiation.
  • Conversely, Ser-18 phosphorylation was not required for ATM-dependent cellular resistance in cells exposed to IR.
  • Efficient acetylation of the p53 C terminus in response to DNA damage proceeded independently of Ser-18 phosphorylation.

Conclusions:

  • Murine p53 Ser-18 phosphorylation is a critical regulatory step for the full DNA damage response mediated by p53.
  • The study highlights distinct roles for Ser-18 phosphorylation in p53-mediated responses versus ATM-dependent cellular resistance.
  • p53 C-terminal acetylation occurs independently of Ser-18 phosphorylation, suggesting alternative regulatory pathways in DNA damage response.

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

Purification of Ubiquitinated p53 Proteins from Mammalian Cells10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

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.
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.
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...
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...
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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...