Related Experiment Video

Updated: May 13, 2026

Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis
12:55

Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis

Published on: February 16, 2015

A myosin-Va tail fragment sequesters dynein light chains leading to apoptosis in melanoma cells

T C Izidoro-Toledo1, A C Borges, D D Araújo

  • 1Department of Cellular and Molecular Biology and Pathogenic Bioagents, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

Cell Death & Disease
|March 23, 2013
PubMed

Insights

Myosin-Va tail fragments induce melanoma cell death by triggering apoptosis. This peptide sequesters DLC proteins, releasing Bmf and Bim to activate cell death, and reduces tumor growth in mice.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Myosin-Va is implicated in apoptosis regulation by sequestering Bmf to the cytoskeleton via DLC2.
  • Cytoskeletal disruptions release Bmf, enabling it to inhibit pro-survival Bcl2 proteins.

Purpose of the Study:

  • To investigate the role of a myosin-Va medial tail fragment (MVaf) in melanoma cell apoptosis.
  • To elucidate the mechanism by which MVaf induces apoptosis and its potential as an anti-cancer therapeutic.

Main Methods:

  • Overexpression of MVaf in melanoma cells.
  • Analysis of apoptotic markers (morphological, molecular, caspase activation, DNA fragmentation).
  • Co-immunoprecipitation to study protein interactions (MVaf, DLCs, Bmf).
  • Assessment of apoptosis in MEFs lacking specific apoptotic proteins (Bim, Bmf, Bax, Bak).
  • In vivo studies using B16-F10 melanoma xenografts in mice.

Main Results:

  • MVaf overexpression induced significant melanoma cell death via apoptosis.
  • MVaf directly bound DLCs, but this complex did not bind Bmf.
  • Overexpression of DLC2 reduced MVaf-induced apoptosis.
  • MEFs deficient in Bim/Bmf or Bax/Bak showed reduced sensitivity to MVaf.
  • MVaf expression suppressed B16-F10 solid tumor growth in mice.

Conclusions:

  • MVaf induces apoptosis by sequestering DLC2 and DLC1, leading to the release and activation of Bmf and Bim.
  • The intrinsic apoptotic pathway plays a crucial role in MVaf-mediated cell death.
  • MVaf demonstrates potential as an apoptosis-inducing agent for cancer research and therapy.

More Related Videos

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells06:09

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

Published on: June 7, 2019

Flow Cytometric Analysis of Apoptotic Biomarkers in Actinomycin D-Treated SiHa Cervical Cancer Cells13:53

Flow Cytometric Analysis of Apoptotic Biomarkers in Actinomycin D-Treated SiHa Cervical Cancer Cells

Published on: August 26, 2021

Related Concept Videos

Overview of Myosin Structure and Function01:15

Overview of Myosin Structure and Function

Myosins are a family of molecular motor proteins, first identified in the skeletal muscles, where they are responsible for muscle contraction. Along with their role in muscle contraction, these proteins also play a role in the intracellular transport of molecules and vesicles. There are twenty-four classes of myosins based on their domain sequence and organization. Of the twenty-four, six classes (Myosin I, Myosin II, Myosin V, Myosin VI, Myosin VII, and Myosin X)  have been well characterized.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Microtubule Associated Motor Proteins01:32

Microtubule Associated Motor Proteins

Eukaryotic cells have different motor proteins for transporting various cargo within the cell. These motor proteins differ based on the filament they associate with, the direction they move within the cell, and the type of cargo they transport. Motor proteins that associate with microtubules are known as microtubule-associated motor proteins. There are two families of microtubule-associated motor proteins —Kinesins and Dyneins. Both these proteins assist in the transport of cellular cargos...
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...
Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
Role of Myosin in Cell Migration01:18

Role of Myosin in Cell Migration

Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
Myosin II  is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction. It is...