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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...
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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

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Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Small molecules that bind the Mdm2 RING stabilize and activate p53.

Patricia Roxburgh1, Andreas K Hock, Michael P Dickens

  • 1The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.

Carcinogenesis
|February 4, 2012
PubMed
Summary
This summary is machine-generated.

New 5-deazaflavin analogs activate the tumor suppressor p53 by inhibiting MDM2

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Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • p53 is a crucial tumor suppressor.
  • MDM2 negatively regulates p53 activity.
  • Targeting MDM2 is a therapeutic strategy for wild-type p53 tumors.

Purpose of the Study:

  • To analyze synthetic 5-deazaflavin analogs as potential MDM2 inhibitors.
  • To investigate the mechanism of action of these analogs.

Main Methods:

  • Surface plasmon resonance to assess binding to MDM2 RING.
  • Cellular assays to evaluate p53 ubiquitination, stabilization, and target gene expression.

Main Results:

  • Active 5-deazaflavin analogs bind to the MDM2 RING.
  • These compounds inhibit p53 ubiquitination and stabilize p53.
  • Increased p53 target gene expression and cell cycle effects were observed.

Conclusions:

  • 5-deazaflavin analogs activate p53 via a novel mechanism.
  • Inhibition of MDM2 E3 ligase activity by binding to the MDM2 RING is demonstrated.