Related Experiment Video

Updated: Jul 18, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Acetylation of the p53 DNA-binding domain regulates apoptosis induction

Stephen M Sykes1, Hestia S Mellert, Marc A Holbert

  • 1Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

Molecular Cell
|December 26, 2006
PubMed

Insights

p53 acetylation at lysine 120 (K120) is a new posttranslational modification crucial for tumor suppression. This modification, catalyzed by hMOF and TIP60, is vital for p53-mediated apoptosis and distinguishing its functions.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • The tumor suppressor protein p53 plays a critical role in preventing cancer by inducing apoptosis.
  • Posttranslational modifications of p53 significantly influence its diverse cellular functions.

Purpose of the Study:

  • To identify and characterize novel posttranslational modifications of p53.
  • To investigate the role of p53 acetylation at lysine 120 (K120) in regulating its apoptotic and cell-cycle arrest functions.

Main Methods:

  • Site-directed mutagenesis to create K120R p53.
  • Western blotting and immunoprecipitation to detect p53 acetylation.
  • Quantitative PCR to assess target gene transcription.
  • Chromatin immunoprecipitation to determine protein localization.

Main Results:

  • Acetylation of p53 at K120, catalyzed by hMOF and TIP60, occurs rapidly after DNA damage.
  • The K120R mutation impairs p53-mediated apoptosis by selectively blocking proapoptotic gene transcription (BAX, PUMA) while sparing cell-cycle arrest genes (p21, hMDM2).
  • Depletion of hMOF/TIP60 or the K120R mutation prevents the accumulation of acetyl-p53 at proapoptotic gene promoters.

Conclusions:

  • K120 acetylation is a critical modification that distinguishes p53's apoptotic and cell-cycle arrest functions.
  • This modification is essential for effective tumor suppression by p53.
  • Dysregulation of K120 acetylation, as seen in cancer mutations, compromises p53's apoptotic 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

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

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.
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...
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.