Related Experiment Video

Updated: Aug 7, 2026

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

Evidence against a functional site for Bcl-2 downstream of caspase cascade in preventing apoptosis

N Yasuhara1, S Sahara, S Kamada

  • 1Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Suita, Japan.

Oncogene
|November 19, 1997
PubMed

Insights

Bcl-2 and Bcl-xL proteins do not prevent apoptosis induced by active caspases. This finding clarifies that these Bcl-2 family proteins do not function downstream of the caspase cascade in cell death pathways.

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Apoptotic cell death is regulated by caspases and Bcl-2 family proteins.
  • Bcl-2 is known to block caspase activation, but its role downstream of caspases is unclear.

Purpose of the Study:

  • To investigate the role of Bcl-2 and Bcl-xL in apoptosis downstream of the caspase cascade.
  • To determine if Bcl-2 and Bcl-xL can prevent apoptosis induced by active caspases.

Main Methods:

  • Microinjection of purified active caspase-3 and caspase-1 into cell cytoplasm.
  • Overexpression of Bcl-2 and Bcl-xL to sufficient levels to block other apoptotic pathways.

Main Results:

  • Microinjected active caspase-3 and caspase-1 induced apoptosis.
  • Overexpressed Bcl-2 and Bcl-xL failed to prevent apoptosis induced by active caspases.
  • These results were observed even when Bcl-2/Bcl-xL were sufficient to block Fas-mediated apoptosis.

Conclusions:

  • Bcl-2 and Bcl-xL do not exert anti-apoptotic effects downstream of the caspase cascade.
  • The anti-apoptotic function of Bcl-2 and Bcl-xL appears to be primarily upstream of caspase activation.

More Related Videos

Examining BCL-2 Family Function with Large Unilamellar Vesicles08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

Related Concept Videos

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 reduction of the tissue.
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 cells.
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...
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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...