Related Experiment Video

Updated: Jun 6, 2026

CD Spectroscopy to Study DNA-Protein Interactions
06:48

CD Spectroscopy to Study DNA-Protein Interactions

Published on: February 10, 2022

c-Abl phosphorylation of Mdm2 facilitates Mdm2-Mdmx complex formation

David L Waning1, Jason A Lehman, Christopher N Batuello

  • 1Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

The Journal of Biological Chemistry
|November 18, 2010
PubMed

Insights

Optimal Mdm2-Mdmx complex formation, crucial for p53 regulation, requires c-Abl kinase phosphorylation of Mdm2. This phosphorylation is vital for Mdmx ubiquitination and subsequent p53 activation following DNA damage.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Oncology

Background:

  • Mdm2 and Mdmx are oncoproteins that regulate p53 stability through ubiquitination.
  • Mdm2-Mdmx complex formation is predicted to modulate Mdm2 ligase activity, but the mechanism is unknown.
  • Phosphorylation of Mdm2 and Mdmx occurs during DNA damage to protect p53.

Purpose of the Study:

  • To elucidate the mechanism regulating Mdm2-Mdmx complex formation.
  • To investigate the role of c-Abl kinase in Mdm2-Mdmx complex formation and p53 activation.

Main Methods:

  • In vitro and in vivo biochemical assays.
  • Phosphorylation studies using Mdm2 and Mdmx.
  • Analysis of Mdm2-Mdmx complex formation and p53 ubiquitination.
  • Experiments using c-Abl(-/-) knock-out murine embryonic fibroblasts.

Main Results:

  • c-Abl phosphorylation of Mdm2 is essential for optimal Mdm2-Mdmx complex formation.
  • Abl phosphorylation of Mdm2 is required for efficient Mdmx ubiquitination.
  • Reduced Mdmx ubiquitination and impaired p53 induction were observed in c-Abl(-/-) cells.
  • A direct link between c-Abl signaling and Mdm2-Mdmx complex formation was established.

Conclusions:

  • Genotoxic stress-activated c-Abl kinase signaling directly regulates Mdm2-Mdmx complex formation.
  • This pathway represents a critical regulatory mechanism for p53 activation in response to DNA damage.

More Related Videos

Resolving Affinity Purified Protein Complexes by Blue Native PAGE and Protein Correlation Profiling09:35

Resolving Affinity Purified Protein Complexes by Blue Native PAGE and Protein Correlation Profiling

Published on: April 1, 2017

Associated Chromosome Trap for Identifying Long-range DNA Interactions14:49

Associated Chromosome Trap for Identifying Long-range DNA Interactions

Published on: April 23, 2011

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...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
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...