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Puckered, a Drosophila MAPK phosphatase, ensures cell viability by antagonizing JNK-induced apoptosis

Donald G McEwen1, Mark Peifer

  • 1Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA. mcewen@uthscsa.edu

Development (Cambridge, England)
|August 5, 2005
PubMed

Insights

Puckered (Puc), a Jun N-terminal kinase (JNK)-specific phosphatase, prevents embryonic apoptosis by regulating JNK signaling. Puc also influences radiation-induced apoptosis and tissue overgrowth, highlighting its role in developmental balance.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Background:

  • Mitogen-activated protein kinase phosphatases (MKPs) regulate MAPKs but functional redundancy in vertebrates complicates specific MKP studies.
  • Puckered (Puc) is the only Jun N-terminal kinase (JNK)-specific MKP in Drosophila, making it a model for studying MKP function.

Purpose of the Study:

  • To characterize the function of Puc, a JNK-specific MKP, in Drosophila embryonic and imaginal disc development.
  • To elucidate the role of JNK signaling in apoptosis, particularly in response to gamma irradiation and during normal development.

Main Methods:

  • Examined Puc function in Drosophila embryos and imaginal discs.
  • Investigated JNK signaling pathways, including p53-dependent regulation and interactions with Reaper and effector caspases.
  • Assessed the impact of JNK signaling on apoptosis and tissue overgrowth.

Main Results:

  • Puc acts as an anti-apoptotic factor by inhibiting basal JNK signaling in epithelial cells.
  • Gamma irradiation upregulates JNK activity and Puc expression in a p53-dependent manner.
  • JNK signaling is crucial for both normal developmental apoptosis and radiation-induced apoptosis, acting upstream of caspases.
  • Inhibition of cell death can lead to JNK-mediated tissue overgrowth.

Conclusions:

  • MKPs, exemplified by Puc, are critical regulators of the balance between cell proliferation, differentiation, and apoptosis during development.
  • JNK signaling, modulated by Puc, plays a central role in diverse cellular processes, from development to stress response.
  • Understanding MKP function is key to comprehending developmental regulation and potential therapeutic strategies for diseases involving aberrant cell death or proliferation.

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