Related Experiment Video

Updated: Apr 6, 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

9.5K

Evidence for anti-apoptotic roles of proteasome activator 28γ via inhibiting caspase activity

Anja Moncsek1, Melanie Gruner, Hannes Meyer

  • 1Department of Biochemistry, Faculty of Natural Sciences, Brandenburg Technical University Cottbus-Senftenberg (BTU C-S), Großenhainer Str. 57, 01968, Senftenberg, Germany.

Apoptosis : an International Journal on Programmed Cell Death
|July 24, 2015
PubMed

Insights

Proteasome activator PA28γ (REGγ) inhibits apoptosis by regulating p53 and caspase activity. This study confirms PA28γ

Area of Science:

  • Cellular biology
  • Molecular biology
  • Cancer research

Background:

  • Proteasome activator PA28γ (REGγ) has known anti-apoptotic functions.
  • PA28γ enhances Mdm2-p53 interaction, promoting p53 degradation.
  • The precise role of PA28γ in apoptosis regulation requires further investigation.

Purpose of the Study:

  • To confirm the role of proteasome activator PA28γ as an anti-apoptotic regulator.
  • To investigate the influence of PA28γ on apoptosis hallmarks like p53 phosphorylation and caspase activation.
  • To elucidate the interplay between PA28γ and caspases in cellular apoptosis.

Main Methods:

  • Overexpression of the PA28γ-encoding gene (PSME3) in mouse fibroblasts.
  • Silencing of the PSME3 gene in human adenocarcinoma cells.
  • Assessment of apoptosis hallmarks, including p53 phosphorylation and caspase activation, following UV-C or butyrate stimulation.

Main Results:

  • Cellular PA28γ levels correlate with sensitivity to apoptosis.
  • PA28γ influences p53 phosphorylation and caspase activation.
  • PA28γ and caspases exhibit mutual regulation; PA28γ overexpression inhibits caspase activity and processing.
  • Overexpression of PA28γ leads to nuclear accumulation of transcriptionally active p53.

Conclusions:

  • Proteasome activator PA28γ acts as an anti-apoptotic regulator.
  • PA28γ-mediated caspase inhibition can overcome pro-apoptotic signaling, even in p53-dependent pathways.
  • PA28γ plays a significant role in cellular resistance to apoptosis.

More Related Videos

Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis12:55

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

Published on: February 16, 2015

18.8K
Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

3.9K

Related Concept Videos

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...
14.6K
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...
9.2K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.4K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
17.0K
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
2.0K
The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
10.6K