Related Experiment Video

Updated: Apr 27, 2026

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

363

Mutant p53 gains new function in promoting inflammatory signals by repression of the secreted interleukin-1 receptor

V Ubertini1, G Norelli1, D D'Arcangelo2

  • 1Experimental Oncology Laboratories, Regina Elena National Cancer Institute, Rome, Italy.

Oncogene
|July 8, 2014
PubMed

Insights

Mutant p53 (mutp53) promotes cancer by suppressing the anti-inflammatory interleukin-1 receptor antagonist (IL1RN). This suppression, involving direct promoter binding and MAFF interaction, creates a pro-inflammatory environment, driving tumor malignancy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • The TP53 tumor-suppressor gene is frequently mutated in human cancers.
  • Gain-of-function (GOF) mutations in p53 can confer novel oncogenic functions, promoting tumor malignancy.
  • A chronic pro-inflammatory tumor microenvironment is associated with increased cancer progression.

Purpose of the Study:

  • To investigate the role of mutant p53 (mutp53) in regulating the expression of the anti-inflammatory cytokine secreted interleukin-1 receptor antagonist (sIL-1Ra).
  • To elucidate the molecular mechanisms by which mutp53 influences sIL-1Ra production and its impact on tumor malignancy.
  • To determine if sIL-1Ra suppression by mutp53 contributes to a pro-inflammatory tumor microenvironment.

Main Methods:

  • Assessed sIL-1Ra production in cancer cell conditioned media comparing mutant p53 (mutp53) and wild-type p53 (wtp53) expressing cells.
  • Performed chromatin immunoprecipitation (ChIP) assays to investigate mutp53 binding to the sIL-1Ra promoter.
  • Utilized co-immunoprecipitation to examine the interaction between mutp53 and the transcriptional co-repressor MAFF.

Main Results:

  • Mutant p53, but not wild-type p53, significantly suppresses the production of sIL-1Ra in cancer cells.
  • Mutant p53 directly binds to the promoter region of the IL1RN gene (encoding sIL-1Ra).
  • The suppression of sIL-1Ra by mutp53 requires its physical interaction with the transcriptional co-repressor MAFF.

Conclusions:

  • Secreted interleukin-1 receptor antagonist (sIL-1Ra) is identified as a novel target gene of mutant p53.
  • Suppression of sIL-1Ra by mutp53 contributes to a chronic pro-inflammatory tumor microenvironment.
  • Mutant p53-mediated sIL-1Ra suppression is a mechanism promoting tumor malignancy.

More Related Videos

Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

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

Published on: August 4, 2019

8.9K
Purification of Ubiquitinated p53 Proteins from Mammalian Cells10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.6K

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...
4.0K
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...
4.6K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
3.2K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.4K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
10.1K
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
12.4K