Related Experiment Video
Updated: Jul 29, 2026
09:18
Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
14-3-3 inhibits Bad-induced cell death through interaction with serine-136
S C Masters1, H Yang, S R Datta
1Graduate Program in Molecular and Systems Pharmacology, Emory University School of Medicine, Atlanta, Georgia, USA.
Molecular Pharmacology
|November 28, 2001
Summary
14-3-3 proteins regulate cell death by binding to the proapoptotic protein Bad. Phosphorylation at serine 136 is critical for this interaction, while serine 112 appears dispensable for 14-3-3 binding and Bad function.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- 14-3-3 proteins are key regulators of cell signaling pathways.
- Dysregulated apoptosis is implicated in various diseases.
- The proapoptotic protein Bad is a target of 14-3-3 proteins.
Purpose of the Study:
- To elucidate the role of specific phosphorylation sites on Bad in mediating 14-3-3 binding.
- To understand the contribution of these sites to the inhibition of Bad-induced apoptosis.
Main Methods:
- In vitro binding assays.
- Yeast and mammalian cell-based interaction studies.
- Site-directed mutagenesis of Bad phosphorylation sites (S112 and S136).
Main Results:
- 14-3-3/Bad interaction is dependent on phosphorylated serine 136 (S136) of Bad.
- Mutation of S112 did not affect 14-3-3 binding to Bad.
- 14-3-3 effectively abrogated cell death induced by wild-type and S112A Bad, but not S136A Bad.
Conclusions:
- Phosphorylation of S136 is essential for 14-3-3 to inhibit Bad's proapoptotic activity.
- S112 phosphorylation may regulate a separate, 14-3-3-independent pathway.
- These findings highlight the critical role of S136 phosphorylation in 14-3-3-mediated apoptosis regulation.
Related Concept Videos
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
01:24Caspases
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.
01:17The 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...
01:31The 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...
01:20The JAK-STAT Signaling Pathway
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...
01:16Cellular Injury IV: Necrosis
Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...