Related Experiment Video

Updated: Oct 21, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

9.7K

p53 is functionally inhibited in clear cell renal cell carcinoma (ccRCC): a mechanistic and correlative investigation

Karoline Diesing1, Silvia Ribback2, Stefan Winter3,4

  • 1Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, E17475, Greifswald, Germany.

Journal of Cancer Research and Clinical Oncology
|September 9, 2021
PubMed
Abstract

Insights

Wildtype p53 is functionally inhibited in clear cell renal cell carcinoma (ccRCC), despite rare mutations. Investigating mechanisms of this inhibition may reveal new therapeutic targets for ccRCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Clear cell renal cell carcinoma (ccRCC) rarely exhibits p53 mutations.
  • Overexpression of p53 in ccRCC has been associated with poorer patient prognosis.

Purpose of the Study:

  • To investigate the distinct role of p53 in ccRCC using comprehensive genomic, proteomic, and functional analyses.
  • To elucidate the mechanisms behind p53's functional inhibition in ccRCC.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) data for p53 genomic and proteomic profiles.
  • Tissue microarray (TMA) study to correlate p53 and phosphorylated p53 (pp53) with clinical outcomes.
  • In vitro experiments to assess p53 function, isoforms, and post-translational modifications in ccRCC cell lines.

Main Results:

  • Confirmed low somatic mutation rates for p53 in ccRCC.
  • Elevated p53 protein levels correlated with poor prognosis, while mRNA levels showed complex associations with survival.
  • In vitro studies indicated functional inhibition of p53 in ccRCC cells, as evidenced by sustained proliferation and transcriptional activity post-irradiation despite induced p53 and pp53 levels.

Conclusions:

  • Wildtype p53 is functionally inhibited in ccRCC, despite its low mutation rate.
  • Understanding the mechanisms of p53 functional inhibition presents potential therapeutic strategies for ccRCC.
Keywords:
BiomarkerRenal cell carcinomaThe Cancer Genome AtlasTumor suppressor genep53

More Related Videos

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method09:32

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method

Published on: September 10, 2017

11.2K
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers12:22

The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers

Published on: January 22, 2013

33.8K

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...
4.7K
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.
36.7K
DNA Damage can Stall the Cell Cycle02:37

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...
9.6K
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...
5.1K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.4K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.3K