Related Experiment Video

Updated: Jan 23, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

9.4K

Tetramer formation by the caspase-activated fragment of the Par-4 tumor suppressor

Andrea M Clark1, Komala Ponniah1, Meghan S Warden1

  • 1Department of Chemistry and Biochemistry, Old Dominion University, Norfolk, VA, USA.

The FEBS Journal
|June 10, 2019
PubMed

Insights

The prostate apoptosis response-4 (Par-4) tumor suppressor

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Prostate apoptosis response-4 (Par-4) is a tumor suppressor that selectively induces apoptosis in cancer cells.
  • Full-length Par-4 is intrinsically disordered in vitro.
  • Caspase-3 cleavage of Par-4 generates a C-terminal fragment (cl-Par-4) that inhibits pro-survival genes.

Purpose of the Study:

  • To investigate the structure and self-association of the activated C-terminal fragment of Par-4 (cl-Par-4).
  • To understand how cellular environment affects cl-Par-4 structure and aggregation.

Main Methods:

  • Circular dichroism (CD) spectroscopy
  • Dynamic light scattering (DLS)
  • Intrinsic tyrosine fluorescence
  • Size exclusion chromatography with multi-angle light scattering (SEC-MALS)

Main Results:

  • cl-Par-4 aggregates and is disordered at low ionic strength.
  • Increasing ionic strength leads to increased helical structure and reduced aggregation.
  • At high NaCl concentrations, cl-Par-4 forms ordered tetramers.
  • Previous studies showed induced folding at acidic pH.

Conclusions:

  • The in vivo structure and self-association of cl-Par-4 are highly dependent on the cellular environment.
  • Ionic strength and pH significantly influence cl-Par-4's structural state and aggregation.
  • Understanding these environmental effects is crucial for elucidating Par-4's apoptotic function in cancer cells.
Keywords:
apoptosiscoiled coildisorderpar-4tumor suppressor

More Related Videos

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila13:21

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila

Published on: November 27, 2016

9.5K
A Matrigel-Based Tube Formation Assay to Assess the Vasculogenic Activity of Tumor Cells04:00

A Matrigel-Based Tube Formation Assay to Assess the Vasculogenic Activity of Tumor Cells

Published on: September 7, 2011

67.0K

Related Concept Videos

Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

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.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.9K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.4K
Habitat Fragmentation02:31

Habitat Fragmentation

Habitat fragmentation describes the division of a more extensive, continuous habitat into smaller, discontinuous areas. Human activities such as land conversion, as well as slower geological processes leading to changes in the physical environment, are the two leading causes of habitat fragmentation. The fragmentation process typically follows the same steps: perforation, dissection, fragmentation, shrinkage, and attrition.
21.2K
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
13.8K
Formation of Species01:31

Formation of Species

Speciation describes the formation of one or more new species from one or sometimes multiple original species. The resulting species are discrete from the parent species, and barriers to reproduction will typically exist. There are two primary mechanisms, speciation with and without geographic isolation—allopatric and sympatric speciation, respectively.
44.8K
Mass Spectrometry: Alkene Fragmentation00:59

Mass Spectrometry: Alkene Fragmentation

Alkenes lose one electron from the unsaturated π bond upon ionization and form stable molecular ions. Further fragmentation of alkenes occurs through three different reaction pathways. The most prominent fragmentation is the cleavage at the allylic position. The resultant allylic carbocation is resonance stabilized. In the mass spectra of terminal alkenes, this fragment appears at a mass-to-charge ratio of 41. In the internal alkenes, where there are two choices of allylic cleavage, the...
3.6K