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Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
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...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
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 daughter...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...

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Related Experiment Video

Updated: May 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

Mutant B-RAF regulates a Rac-dependent cadherin switch in melanoma.

E Monaghan-Benson1, K Burridge

  • 11] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA [2] Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Oncogene
|December 5, 2012
PubMed
Summary
This summary is machine-generated.

Mutant B-RAF signaling in melanoma promotes cell invasion by altering cell adhesion molecules. This pathway involves downregulation of Tiam1/Rac activity, leading to increased N-cadherin and decreased E-cadherin, driving melanoma

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

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Last Updated: May 16, 2026

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

Published on: March 1, 2024

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Mechanisms of Cancer

Background:

  • Cutaneous melanoma cell invasion into the dermis is critical for progression and prognosis.
  • Mutations in B-RAF are common in melanoma and influence invasive behavior.
  • The precise molecular regulators of melanoma cell invasion remain incompletely understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which mutant B-RAF signaling controls melanoma cell invasion.
  • To investigate the role of cadherin switching in B-RAF-driven melanoma invasion.

Main Methods:

  • Utilized small interfering RNA (siRNA) to deplete mutant B-RAF, Rac1, and Tiam1 in melanoma cells.
  • Quantified changes in N-cadherin and E-cadherin expression levels.
  • Assessed melanoma cell invasive capacity through invasion assays.

Main Results:

  • Mutant B-BRAF signaling induced a cadherin switch, characterized by high N-cadherin and low E-cadherin levels.
  • Depletion of mutant B-RAF reversed this switch, decreasing N-cadherin and increasing E-cadherin.
  • This switch was dependent on the activity of Rac1 and its guanine nucleotide exchange factor, Tiam1.
  • Simultaneous depletion of B-RAF and Rac1/Tiam1 abrogated the invasive phenotype.

Conclusions:

  • Mutant B-RAF signaling suppresses Tiam1/Rac activity, promoting a cadherin switch that enhances melanoma cell invasion.
  • Targeting the B-RAF/Tiam1/Rac1 pathway offers a potential therapeutic strategy for invasive melanoma.