Related Experiment Video

Updated: Jun 27, 2025

In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity
09:45

In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity

Published on: January 29, 2018

9.4K

Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in

Konstantinos V Floros, Carter K Fairchild, Jinxiu Li

    Biorxiv : the Preprint Server for Biology
    |May 7, 2024
    PubMed

    Insights

    Targeting the SUMOylation pathway with TAK-981 inhibits synovial sarcoma (SS) by restoring chromatin remodeling complexes. This approach shows promise for treating SS and synergizes with chemotherapy.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Cancer Genetics

    Background:

    • Synovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein, leading to resistance to current therapies.
    • SS18::SSX alters ATP-dependent chromatin remodeling BAF (mammalian SWI/SNF) complexes, promoting tumorigenesis through a specific transcriptional program.

    Purpose of the Study:

    • To investigate the therapeutic potential of targeting the SUMOylation pathway in SS.
    • To elucidate the mechanism of action of the SAE1/2 inhibitor TAK-981 in SS.

    Main Methods:

    • Treatment of human and mouse SS models with TAK-981.
    • Analysis of chromatin remodeling complex composition and transcriptional changes.
    • Assessment of DNA damage and cell death induction.
    • Evaluation of synergistic effects with cytotoxic chemotherapy.

    Main Results:

    • SS18::SSX activates SUMOylation; SSs are sensitive to TAK-981.
    • TAK-981 de-SUMOylates SMARCE1, restoring canonical BAF (cBAF) complexes.
    • Restored cBAF shifts transcription away from the SS18::SSX-driven program, inducing DNA damage and cell death.
    • TAK-981 demonstrated tumor inhibition in SS models and synergized with chemotherapy for tumor regression.

    Conclusions:

    • Targeting the SUMOylation pathway represents a therapeutic vulnerability in SS.
    • TAK-981 restores cBAF complexes and blocks oncogenic transcription, offering a novel treatment strategy.
    • The in-clinic drug TAK-981 is positioned as a potential therapy for synovial sarcoma.

    More Related Videos

    Saccharomyces cerevisiae Metabolic Labeling with 4-thiouracil and the Quantification of Newly Synthesized mRNA As a Proxy for RNA Polymerase II Activity09:21

    Saccharomyces cerevisiae Metabolic Labeling with 4-thiouracil and the Quantification of Newly Synthesized mRNA As a Proxy for RNA Polymerase II Activity

    Published on: October 22, 2018

    9.1K
    SUMO-Binding Entities SUBEs as Tools for the Enrichment, Isolation, Identification, and Characterization of the SUMO Proteome in Liver Cancer08:29

    SUMO-Binding Entities SUBEs as Tools for the Enrichment, Isolation, Identification, and Characterization of the SUMO Proteome in Liver Cancer

    Published on: November 1, 2019

    7.1K

    Related Concept Videos

    mRNA Stability and Gene Expression02:51

    mRNA Stability and Gene Expression

    The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
    Cis-acting Elements involved in mRNA stability
    5.6K
    RNA Splicing01:32

    RNA 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...
    56.3K
    Cytoskeletal Accessory Proteins01:13

    Cytoskeletal Accessory Proteins

    The cytoskeleton is an essential cell component that plays several structural and functional roles. However, the filaments that make up the cytoskeleton cannot function independently and depend on the accessory or ancillary proteins to effectively carry out their function. Accessory proteins associate with cytoskeletal filaments and their monomers, aiding filament formation and function. They also help in the cross-communication among cytoskeletal filaments. Cytoskeletal accessory proteins are...
    3.1K
    Covalently Linked Protein Regulators02:04

    Covalently Linked Protein Regulators

    Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
    These groups modify specific amino acids in a protein....
    6.8K
    Regulation of Expression at Multiple Steps01:23

    Regulation of Expression at Multiple Steps

    The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
    893
    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...
    4.5K