Related Experiment Video

Updated: Aug 8, 2025

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

6.5K

RAS and PP2A activities converge on epigenetic gene regulation

Anna Aakula1, Mukund Sharma1, Francesco Tabaro2

  • 1Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.

Life Science Alliance
|March 1, 2023
PubMed

Insights

RAS hyperactivity and protein phosphatase 2A (PP2A) inhibition converge on epigenetic regulators in human cancers. This convergence impacts gene expression and chromatin states, offering new therapeutic targets for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • RAS-mediated cell transformation necessitates inhibition of the tumor suppressor protein phosphatase 2A (PP2A).
  • The specific phosphoprotein targets and cellular pathways influenced by RAS and PP2A in cancer remain incompletely understood.

Purpose of the Study:

  • To systematically analyze phosphoprotein targets and cellular processes where RAS and PP2A activities intersect in human cancers.
  • To investigate the role of epigenetic gene regulation in the convergence of RAS and PP2A signaling.

Main Methods:

  • Phosphoproteomic analysis to identify co-regulated phosphosites.
  • Validation of identified phosphoregulation on key epigenetic proteins (e.g., HDAC1/2, RNF168, TP53BP1).
  • Assays to assess chromatin recruitment, protein interactions, gene expression, and epigenetic reporter activity.

Main Results:

  • Phosphosites co-regulated by RAS and PP2A are significantly enriched in proteins involved in epigenetic gene regulation.
  • RAS and PP2A co-regulate phosphorylation sites on epigenetic modifiers including HDAC1/2, KDM1A, MTA1/2, RNF168, and TP53BP1.
  • RAS activation and PP2A inhibition lead to epigenetic reporter derepression, oncogenic transcription activation, increased euchromatin, and decreased DNA methylation.

Conclusions:

  • Epigenetic protein complexes represent a critical convergence point for RAS hyperactivity and PP2A inhibition in cancer.
  • The findings provide a valuable resource for research into phosphoregulation of epigenetic gene regulation in cancer and other RAS/PP2A-related processes.

More Related Videos

A Method to Study de novo Formation of Chromatin Domains07:34

A Method to Study de novo Formation of Chromatin Domains

Published on: August 23, 2019

5.5K
In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing10:44

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing

Published on: May 5, 2023

1.5K

Related Concept Videos

Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
3.1K
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.3K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.4K
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.5K
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
7.1K
Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
8.3K