Related Experiment Video
Updated: Aug 17, 2026

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
Published on: November 27, 2016
B56-associated protein phosphatase 2A is required for survival and protects from apoptosis in Drosophila melanogaster
Xinghai Li1, Anne Scuderi, Anthea Letsou
1Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112-5550, USA.
Abstract:
Protein phosphorylation and specific protein kinases can initiate signal transduction pathways leading to programmed cell death. The specific protein phosphatases regulating apoptosis have been more elusive. Using double-stranded RNA-mediated interference (RNAi), the role of protein phosphatase 2A (PP2A) in cellular signaling was investigated. Knockdown of A or C subunits individually or of combined B subunits led to concurrent loss of nontargeted PP2A subunits, suggesting that PP2A is an obligate heterotrimer in vivo. Global knockdown of PP2A activity or specific loss of redundant B56 regulatory subunits caused cell death with the morphological and biochemical changes characteristic of apoptosis in cultured S2 cells. B56:PP2A-regulated apoptosis required caspases and the upstream regulators dark, reaper, head involution defective, and dp53. In Drosophila embryos, knockdown of B56-regulated PP2A activity resulted in apoptosis and failure of gastrulation, an effect that was blocked by concurrent RNAi of the caspase DRICE: B56-regulated PP2A activity appears to be required upstream of dp53 to maintain a critical proapoptotic substrate in a dephosphorylated, inactive state, thereby preventing apoptosis in Drosophila S2 cells.
Insights
Protein phosphatase 2A (PP2A) is essential for preventing apoptosis by regulating key signaling pathways. Loss of PP2A activity triggers programmed cell death, highlighting its critical role in cellular homeostasis.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Protein phosphorylation by kinases initiates cell death signaling, but phosphatases regulating apoptosis remain less understood.
- Protein Phosphatase 2A (PP2A) is a key enzyme in cellular signaling pathways.
Purpose of the Study:
- To investigate the role of Protein Phosphatase 2A (PP2A) in cellular signaling and apoptosis using RNA interference (RNAi).
- To elucidate the regulatory mechanisms of PP2A in programmed cell death.
Main Methods:
- Utilized double-stranded RNA-mediated interference (RNAi) to knockdown PP2A subunits in Drosophila S2 cells and embryos.
- Analyzed morphological and biochemical changes associated with apoptosis.
- Investigated the requirement of caspases and upstream regulators like dark, reaper, head involution defective, and dp53.
Main Results:
- PP2A functions as an obligate heterotrimer in vivo.
- Knockdown of PP2A activity or B56 regulatory subunits induced apoptosis in S2 cells.
- B56-regulated PP2A activity is required upstream of dp53 to prevent apoptosis by maintaining a proapoptotic substrate in an inactive state.
- Knockdown of PP2A in Drosophila embryos caused apoptosis and gastrulation defects, which were rescued by caspase inhibition.
Conclusions:
- PP2A, particularly the B56-containing forms, plays a crucial role in preventing apoptosis in Drosophila.
- PP2A acts upstream of dp53 in a pathway that regulates proapoptotic substrates.
- Understanding PP2A's role in apoptosis is vital for comprehending cell death regulation.
Related Concept Videos
Negative Regulator Molecules
DNA Damage can Stall the Cell Cycle
Abnormal Proliferation
The Extrinsic Apoptotic Pathway
The Intrinsic Apoptotic Pathway
DNA Damage Can Stall the Cell Cycle

