Related Experiment Video

Updated: Aug 8, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Nucleolin inhibits Hdm2 by multiple pathways leading to p53 stabilization

A Saxena1, C J Rorie, D Dimitrova

  • 1Department of Biochemistry and New York University Cancer Institute, New York University School of Medicine, New York, NY 10016, USA.

Oncogene
|June 6, 2006
PubMed

Insights

Nucleolin protein levels directly impact p53 protein amounts by inhibiting Hdm2, a key regulator. This finding reveals nucleolin

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Nucleolin is involved in rRNA processing and DNA replication inhibition.
  • Its role in unstressed cells and p53 regulation is not fully understood.

Purpose of the Study:

  • To investigate the effect of nucleolin on p53 protein levels in unstressed cells.
  • To elucidate the mechanism by which nucleolin influences p53 stability.
  • To determine the functional consequences of nucleolin-mediated p53 regulation.

Main Methods:

  • Western blotting to assess protein levels (nucleolin, p53, Hdm2, p21).
  • Immunoprecipitation assays to study protein-protein interactions (nucleolin-Hdm2).
  • Ubiquitination assays to measure p53 and Hdm2 ubiquitination.
  • Cell proliferation and apoptosis assays.

Main Results:

  • Nucleolin levels directly correlate with p53 protein levels in unstressed cells.
  • Nucleolin binds to Hdm2, inhibiting both p53 and Hdm2 ubiquitination.
  • Nucleolin reduces Hdm2 protein levels through mechanisms beyond inhibiting ligase activity.
  • Increased nucleolin leads to elevated p21(cip1/waf1) expression, reduced proliferation, and increased apoptosis.

Conclusions:

  • Nucleolin acts as a regulator of p53 stability by inhibiting Hdm2.
  • Nucleolin shares functional similarities with the tumor suppressor ARF.
  • Nucleolin may function as a tumor suppressor by upregulating p53 in response to hyperproliferative signals.

More Related Videos

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD108:17

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1

Published on: April 16, 2021

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

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...
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.
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...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...