Related Experiment Video

Updated: Jul 9, 2026

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

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

Published on: June 7, 2019

B-Raf(V600E) signaling deregulates the mitotic spindle checkpoint through stabilizing Mps1 levels in melanoma cells

Y Cui1, T M Guadagno

  • 1Molecular Oncology Program, Cutaneous Oncology Division, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

Oncogene
|December 12, 2007
PubMed

Insights

The B-Raf(V600E) mutation in melanoma stabilizes Mps1 protein levels, leading to spindle checkpoint activation and mitotic delay. This highlights a new oncogenic mechanism driven by B-Raf signaling.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cell Cycle Regulation

Background:

  • The B-Raf(V600E) mutation is prevalent in human melanomas, driving tumor growth via the ERK pathway.
  • B-Raf plays a role in spindle formation and mitotic checkpoint control.

Purpose of the Study:

  • To investigate how B-Raf(V600E) signaling affects the spindle checkpoint in melanoma.
  • To elucidate the role of Mps1 (monopolar spindle 1) in B-Raf-driven tumorigenesis.

Main Methods:

  • Introducing B-Raf(V600E) into wild-type melanoma cells.
  • Utilizing RNA interference (RNAi) to reduce B-Raf levels.
  • Employing a MEK inhibitor (U0126) to block ERK signaling.
  • Measuring Mps1 protein levels and activity.
  • Using short interfering RNA (siRNA) to deplete Mps1.

Main Results:

  • B-Raf(V600E) increased Mps1 protein and activity, leading to Mps1 hyperphosphorylation and stabilization.
  • B-Raf reduction or ERK inhibition decreased Mps1 levels.
  • B-Raf(V600E) induced a mitotic delay dependent on elevated Mps1 levels.

Conclusions:

  • B-Raf signaling, through ERK, regulates Mps1 stability.
  • B-Raf(V600E) promotes melanoma oncogenesis by deregulating the spindle checkpoint via Mps1 stabilization.

More Related Videos

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

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

Published on: July 17, 2019

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma08:18

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma

Published on: September 8, 2021

Related Concept Videos

The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
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...
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...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.