Related Experiment Video
Updated: Jul 21, 2026
08:01
The Soft Agar Colony Formation Assay
Published on: October 27, 2014
Beta-catenin interacts with the FUS proto-oncogene product and regulates pre-mRNA splicing
Satoshi Sato1, Masashi Idogawa, Kazufumi Honda
1Chemotherapy Division and Cancer Proteomics Project, National Cancer Center Research Institute, Tokyo, Japan.
Gastroenterology
|October 19, 2005
Summary
Nuclear beta-catenin interacts with RNA-binding proteins, influencing gene expression and alternative splicing in cancer. This suggests the Wnt signaling pathway may drive cancer-related mRNA splicing.
Area of Science:
- Molecular Biology
- Cancer Research
- Proteomics
Background:
- Beta-catenin is a key effector in Wnt signaling, typically activating T-cell factor (TCF)/lymphoid enhancer factor (LEF) transcription factors.
- The precise mechanisms behind beta-catenin's diverse oncogenic functions beyond gene transactivation remain unclear.
- Understanding nuclear beta-catenin's interactions is crucial for elucidating its role in cancer.
Purpose of the Study:
- To investigate the functional properties of nuclear beta-catenin using a proteomics approach.
- To identify proteins interacting with beta-catenin in the nucleus.
- To explore the link between beta-catenin, RNA-binding proteins, and alternative splicing in cancer.
Main Methods:
- Utilized immunoprecipitation and mass spectrometry to identify protein complexes associated with nuclear beta-catenin.
- Analyzed nuclear extracts from the DLD-1 colorectal cancer cell line.
- Performed transient transfection experiments to assess the functional impact of protein interactions.
Main Results:
- Identified physical interactions between beta-catenin and fusion (FUS)/translocated in liposarcoma (TLS), along with other RNA-binding proteins.
- Found a correlation between FUS/TLS expression, beta-catenin accumulation, and intestinal epithelial cell undifferentiation.
- Demonstrated that FUS/TLS suppresses beta-catenin-mediated gene transactivation and that beta-catenin affects mRNA splicing patterns, including inducing a dominant-negative estrogen receptor (ER)-beta variant.
Conclusions:
- Established a novel interaction between beta-catenin, FUS/TLS, and RNA-binding proteins involved in pre-mRNA splicing regulation.
- Proposed that Wnt pathway activation, through beta-catenin, may induce specific mRNA splicing patterns observed in human cancers.
- Highlighted the potential role of the Wnt/beta-catenin pathway in driving cancer-related alternative splicing.
Related Concept Videos
01:32RNA Splicing
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
02:41Chromatin 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...
The chromatin structure, especially...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
02:18Alternative RNA Splicing
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
02:54Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
01:23Catenins
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...