Related Experiment Video
Updated: Mar 17, 2026
08:35
Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
8.4K
An Autoinhibited Dimeric Form of BAX Regulates the BAX Activation Pathway
Thomas P Garner1, Denis E Reyna1, Amit Priyadarshi1
1Department of Biochemistry and Department of Medicine, Albert Einstein Cancer Center, Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Molecular Cell
|July 19, 2016
Summary
Inactive BAX dimers regulate apoptosis by inhibiting BAX activation. This discovery reveals a new mechanism controlling programmed cell death and cellular homeostasis.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- BAX protein is a key regulator of programmed cell death (apoptosis).
- Cytosolic BAX exists in a quiescent monomer form before activation.
- Upon apoptotic stimuli, BAX activates, translocates to mitochondria, and induces cell death.
Purpose of the Study:
- To investigate the conformational states of cytosolic BAX.
- To elucidate the regulatory mechanisms of BAX activation.
- To understand the structural basis of BAX inhibition.
Main Methods:
- Cellular assays
- Biochemical analyses
- Full-length BAX dimer crystal structure determination
Main Results:
- Cytosolic BAX exists in an inactive dimer conformation.
- The inactive dimer structure reveals an asymmetric interaction inhibiting activation.
- Dissociation of the dimer is required for subsequent BAX activation.
Conclusions:
- The conformation of cytosolic BAX regulates apoptosis.
- An unprecedented autoinhibition mechanism for cytosolic BAX was identified.
- This finding provides new insights into the control of programmed cell death.
More Related Videos
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
9.1K
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...
9.1K
02:26NF-κB-dependent Signaling Pathway
10.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
10.2K
01:17The Extrinsic Apoptotic Pathway
9.2K
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...
9.2K
01:20The JAK-STAT Signaling Pathway
13.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
13.7K
01:07MAPK Signaling Cascades
9.1K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.1K
01:18Autophagic Cell Death
4.9K
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...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.9K