BH3-only proteins Noxa, Bik, Bmf, and Bid activate Bax and Bak indirectly when studied in yeast model

Gabriela Gérecová1, Jana Kopanicová, Petra Jaká

  • 1Department of Biochemistry, Faculty of Natural Sciences, Comenius University, Bratislava, Slovak Republic.

FEMS Yeast Research
|September 3, 2013
PubMed

Insights

BH3-only proteins activate cell death by inhibiting antiapoptotic proteins, not directly activating Bax and Bak. This finding clarifies the mechanism of programmed cell death regulation.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The Bcl-2 family regulates programmed cell death.
  • BH3-only proteins are key mediators of apoptosis.
  • The precise mechanism of BH3-only protein action is debated.

Purpose of the Study:

  • To investigate the mechanism by which BH3-only proteins induce cell death.
  • To determine the role of antiapoptotic proteins in BH3-only protein function.

Main Methods:

  • Reconstitution of cell death assays in yeast.
  • Utilizing various BH3-only proteins (Bik, Bmf, Noxa, tBid).
  • Co-expression of proapoptotic and antiapoptotic Bcl-2 family proteins.

Main Results:

  • BH3-only proteins' cell death activity requires both proapoptotic and antiapoptotic Bcl-2 proteins.
  • BH3-only proteins failed to induce cell death in the absence of antiapoptotic proteins.
  • This suggests an indirect activation mechanism.

Conclusions:

  • BH3-only proteins likely activate Bax and Bak indirectly.
  • The primary function of BH3-only proteins involves inhibiting antiapoptotic proteins.
  • This provides a refined understanding of apoptosis regulation.

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...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

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 heterodimer of NF-κB...
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.
Other Stress Responses in Bacteria01:30

Other Stress Responses in Bacteria

Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
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 pro-apoptotic...
Regulation of Bacterial Virulence01:28

Regulation of Bacterial Virulence

Pathogenic bacteria employ a range of regulatory mechanisms to modulate the expression of virulence genes in response to environmental and host-derived signals. These mechanisms ensure that virulence factors are expressed only under favorable conditions, thereby optimizing infection and survival strategies.Mechanisms of Virulence RegulationKey regulatory strategies include:Two-Component Systems: These consist of a membrane-bound sensor kinase and a cytoplasmic response regulator. Environmental...