Related Experiment Video

Updated: Apr 11, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

8.4K

BCL-2 family member BOK promotes apoptosis in response to endoplasmic reticulum stress

Marcos A Carpio1, Michael Michaud1, Wenping Zhou1

  • 1Department of Pathology, Yale School of Medicine, New Haven, CT 06520;

Proceedings of the National Academy of Sciences of the United States of America
|May 28, 2015
PubMed

Insights

B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) protein deletion selectively impairs apoptosis in response to endoplasmic reticulum (ER) stress. This study reveals BOK

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Apoptosis Research

Background:

  • B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) is a BCL-2 family protein homologous to BAX and BAK.
  • Previous studies reported no overt phenotype in Bok-deficient mice, suggesting functional compensation by BAX and BAK.
  • However, BOK's role in apoptosis, particularly under endoplasmic reticulum (ER) stress, remained unclear.

Purpose of the Study:

  • To investigate the specific role of BOK in apoptosis, particularly in response to ER stress.
  • To determine if BOK can compensate for apoptotic defects in BAX and BAK deficient cells.
  • To elucidate the molecular mechanisms underlying BOK's function in ER stress-induced apoptosis.

Main Methods:

  • Generation and analysis of independently developed Bok-deficient (Bok(-/-)) mice and cells.
  • Assessment of apoptotic responses in Bok(-/-) cells and tissues using various stress stimuli, including ER stress agents (thapsigargin, A23187, etc.).
  • Evaluation of mitochondrial apoptotic pathway activation, unfolded protein response (UPR) signaling (ATF4, CHOP), and BAX/BAK compensation.

Main Results:

  • Bok(-/-) cells exhibited selectively reduced apoptosis upon exposure to ER stress stimuli, with intact responses to other apoptotic triggers.
  • Bok(-/-) mice showed resistance to thapsigargin-induced apoptosis in multiple organs.
  • Activation of ATF4 and CHOP was diminished in Bok(-/-) cells and mice, and BAX/BAK could not compensate for the ER stress-induced apoptotic defect.

Conclusions:

  • BOK plays a selective and crucial role in regulating apoptosis specifically in response to ER stress.
  • The deletion of BOK leads to a bona fide apoptotic defect under ER stress conditions.
  • BAX and BAK cannot functionally compensate for BOK's role in ER stress-mediated apoptosis, highlighting BOK's unique contribution.
Keywords:
BCL-2 familyBOKapoptosisendoplasmic reticulum stressunfolded protein response

More Related Videos

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons10:50

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Published on: April 24, 2021

1.4K
Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling08:51

Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling

Published on: June 25, 2015

9.7K

Related Concept Videos

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...
9.3K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.2K
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
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
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
5.7K
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...
17.1K