Related Experiment Videos

Antiproliferative activity of CCN3: involvement of the C-terminal module and post-translational regulation

A M Bleau1, N Planque, N Lazar

  • 1Université Paris7-D. Diderot, UFR de Biochimie, Laboratoire d'Oncologie Virale et Moléculaire, 2 place Jussieu, 75005 Paris, France.

Journal of Cellular Biochemistry
|March 7, 2007
PubMed

Insights

Native CCN3 protein inhibits glioma cell proliferation and accumulates at high cell density. Its secretion is regulated by proteolysis, varying with the cell cycle, and the C-terminal module is key for growth inhibition.

Area of Science:

  • Cell biology
  • Molecular biology
  • Cancer research

Background:

  • Previous studies indicated recombinant CCN3 protein partially inhibits cell proliferation.
  • CCN proteins are involved in regulating cell growth and development.

Purpose of the Study:

  • To investigate the role of native CCN3 protein in regulating glioma cell proliferation.
  • To elucidate the mechanisms of CCN3 secretion and cell cycle regulation.

Main Methods:

  • Utilized glioma cells transfected to secrete native CCN3 protein.
  • Analyzed CCN3 accumulation in cytoplasm and extracellular medium.
  • Investigated CCN3 regulation by post-translational proteolysis and cell cycle.
  • Employed antibodies against CCN3 C-terminal peptide and clones expressing CCN3 fragments.

Main Results:

  • Native CCN3 protein secreted by glioma cells reduces cell proliferation.
  • CCN3 accumulates cytoplasmically and extracellularly at high cell density.
  • CCN3 secretion is regulated by post-translational proteolysis, with accumulation at G2/M phase.
  • CCN3-induced growth inhibition is partially reversible by anti-CCN3 antibodies.
  • The C-terminal (CT) module of CCN3 is sufficient for growth inhibition.

Conclusions:

  • Native CCN3 protein acts as a novel regulator of glioma cell proliferation.
  • CCN3 secretion and accumulation are linked to cell density and cell cycle progression.
  • The CT module of CCN3 plays a critical role in mediating cell growth inhibition.

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
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...