Related Experiment Video

Updated: Jul 10, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

The Wip1 Phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop

Xiongbin Lu1, Ou Ma, Thuy-Ai Nguyen

  • 1Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA. larry@bcm.tmc.edu

Cancer Cell
|October 16, 2007
PubMed

Insights

The phosphatase Wip1 (wild-type p53-induced phosphatase 1) stabilizes Mdm2, promoting the degradation of the tumor suppressor p53. This action regulates the Mdm2-p53 feedback loop, impacting cellular stress responses.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • The tumor suppressor p53 is a critical transcription factor involved in cell cycle arrest and apoptosis in response to cellular stress.
  • Mdm2, an E3 ubiquitin ligase, forms a negative feedback loop with p53 by promoting its proteasomal degradation.

Purpose of the Study:

  • To investigate the role of wild-type p53-induced phosphatase 1 (Wip1) in the regulation of the Mdm2-p53 interaction.
  • To elucidate the mechanism by which Wip1 influences p53 protein levels.

Main Methods:

  • Investigated the interaction between Wip1 and Mdm2.
  • Analyzed the effect of Wip1 on Mdm2 phosphorylation at serine 395.
  • Assessed the impact of Wip1-mediated Mdm2 dephosphorylation on Mdm2 stability and p53 degradation.

Main Results:

  • Wip1 directly interacts with and dephosphorylates Mdm2 at serine 395, a site targeted by ATM kinase.
  • Dephosphorylation of Mdm2 by Wip1 enhances its stability and affinity for p53.
  • Stabilized Mdm2 facilitates p53 ubiquitination and subsequent proteasomal degradation, leading to downregulation of p53 protein levels.

Conclusions:

  • Wip1 acts as a key regulator in the Mdm2-p53 feedback loop by stabilizing Mdm2.
  • Wip1 promotes Mdm2-mediated proteolysis of p53, thereby controlling p53 protein levels.
  • Wip1 functions as a gatekeeper in this crucial regulatory pathway, influencing cellular responses to stress.

More Related Videos

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

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...
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.
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...
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...