Related Experiment Video

Updated: May 22, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

An autoregulatory feedback loop between Mdm2 and SHP that fine tunes Mdm2 and SHP stability

Zhihong Yang1, Li Wang

  • 1Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132, United States.

FEBS Letters
|May 12, 2012
PubMed

Insights

Small heterodimer partner (SHP) stabilizes Mdm2 by blocking its self-ubiquitination. Mdm2 then reduces SHP levels in p53-deficient cells, revealing a novel feedback loop in tumor suppression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Mdm2 negatively regulates tumor suppressor p53.
  • Regulation of Mdm2 stability by tumor suppressors is not well understood.
  • Small heterodimer partner (SHP) acts as a tumor suppressor in liver cancer.

Purpose of the Study:

  • To investigate the regulatory relationship between SHP and Mdm2.
  • To elucidate the mechanism of Mdm2 protein stability regulation by SHP.

Main Methods:

  • Co-immunoprecipitation assays to detect protein interactions.
  • Ubiquitination assays to assess protein modification.
  • Western blotting to analyze protein levels.

Main Results:

  • SHP stabilizes Mdm2 by inhibiting Mdm2 self-ubiquitination.
  • Mdm2 reduces SHP protein levels under p53-deficient conditions.
  • SHP interaction with Mdm2 at K170 is essential for this cross-regulation.

Conclusions:

  • A feedback loop exists between SHP and Mdm2.
  • This interplay is a novel aspect of Mdm2 signaling, impacting its activity and function.
  • SHP-Mdm2 interaction is critical for liver cancer tumor suppression pathways.

More Related Videos

Development and Application of Rapamycin-regulated Tyrosine Phosphatases06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

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...
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
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...
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
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...
The Cell Cycle Control System01:28

The Cell Cycle Control System

The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...