Related Experiment Video

Updated: Jun 19, 2025

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

7.9K

BCL-2 and BOK regulate apoptosis by interaction of their C-terminal transmembrane domains

Tobias B Beigl1, Alexander Paul1, Thomas P Fellmeth2

  • 1Robert Bosch Center for Tumor Diseases, Stuttgart, Germany.

EMBO Reports
|July 24, 2024
PubMed

Insights

The transmembrane domains (TMDs) of BCL-2 proteins mediate interactions, revealing a new mechanism for apoptosis regulation. This discovery highlights TMDs as potential drug targets for cancer therapy.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The BCL-2 protein family regulates apoptosis through interactions between pro- and anti-apoptotic members.
  • Current therapies target the BH3 domain interactions, but evidence suggests transmembrane domains (TMDs) also mediate interactions.

Purpose of the Study:

  • To investigate the role of TMDs in BCL-2 protein interactions and apoptosis regulation.
  • To develop a novel assay for analyzing TMD interactions in living cells.

Main Methods:

  • Developed a split luciferase assay to analyze TMD interactions of BAX, BAK, and BOK with anti-apoptotic BCL-2 proteins in living cells.
  • Utilized molecular dynamics simulations to model TMD dimer and heterotetramer formation.
  • Performed site-directed mutagenesis to assess the functional importance of specific TMD residues.

Main Results:

  • Confirmed homotypic interactions of BAX-TMD.
  • Newly identified interactions between BCL-2-TMD and BOK-TMD at the endoplasmic reticulum.
  • Demonstrated that BCL-2-TMD/BOK-TMD interaction is crucial for BCL-2's inhibition of BOK-induced apoptosis.

Conclusions:

  • TMDs represent a significant, previously underappreciated interaction interface in BCL-2 family-mediated apoptosis.
  • BCL-2-TMD and BOK-TMD interactions are functionally relevant for apoptosis control.
  • BCL-2 protein TMDs offer a novel therapeutic target for modulating apoptosis in diseases like cancer.
Keywords:
ApoptosisBCL-2BOKEndoplasmic ReticulumTransmembrane Domain

More Related Videos

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

9.2K
Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

17.4K

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...
6.4K
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...
6.3K
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...
11.3K
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...
12.4K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.4K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K