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Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Microtubule Associated Proteins (MAPs)01:42

Microtubule Associated Proteins (MAPs)

Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
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Cell Motility through Blebbing

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Related Experiment Video

Updated: Jul 16, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

A molecular glue to take down mutant BRAF.

Leslie K Ferrarelli1

  • 1Science Signaling, AAAS, Washington, DC 20005, USA.

Science Signaling
|July 14, 2026
PubMed
Summary

A novel molecular glue degrader targets mutant BRAF, a key driver in drug-resistant colorectal cancer. This approach works by interfering with messenger RNA (mRNA) splicing, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Colorectal cancer (CRC) frequently harbors mutations in BRAF, leading to aggressive disease.
  • Acquired resistance to BRAF inhibitors remains a significant clinical challenge in CRC treatment.
  • Alternative therapeutic strategies are urgently needed to overcome BRAF-driven drug resistance.

Purpose of the Study:

  • To investigate a novel molecular glue degrader targeting mutant BRAF in drug-resistant CRC models.
  • To elucidate the mechanism of action, focusing on the disruption of mRNA splicing.
  • To assess the therapeutic potential of this approach against resistant colorectal cancer.

Main Methods:

  • Development and characterization of a specific molecular glue degrader.

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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

Related Experiment Videos

Last Updated: Jul 16, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells
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Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells

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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

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Published on: June 7, 2019

  • In vitro and in vivo studies using CRC cell lines and patient-derived xenografts with mutant BRAF.
  • Analysis of mRNA splicing patterns and BRAF protein levels.
  • Assessment of anti-tumor efficacy and resistance mechanisms.

    • Main Results:

    • The molecular glue degrader effectively reduced mutant BRAF protein levels in resistant CRC cells.
    • Disruption of specific mRNA splicing events was identified as the primary mechanism of action.
    • Significant tumor growth inhibition was observed in preclinical models of drug-resistant CRC.

    Conclusions:

    • Molecular glue degraders represent a promising strategy for targeting mutant BRAF in drug-resistant colorectal cancer.
    • Interference with mRNA splicing is a viable mechanism for achieving targeted protein degradation.
    • This approach offers a potential new avenue for overcoming therapeutic resistance in CRC.