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First published online 3 August 2005
doi: 10.1242/dev.01949
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1 Lineberger Comprehensive Cancer Center, The University of North Carolina at
Chapel Hill, Chapel Hill, NC 27599-3280, USA
2 Department of Biology, The University of North Carolina at Chapel Hill, Chapel
Hill, NC 27599-3280, USA
Author for correspondence (e-mail:
mcewen{at}uthscsa.edu)
Accepted 21 June 2005
MAPK phosphatases (MKPs) are important negative regulators of MAPKs in
vivo, but ascertaining the role of specific MKPs is hindered by functional
redundancy in vertebrates. Thus, we characterized MKP function by examining
the function of Puckered (Puc), the sole Drosophila Jun N-terminal
kinase (JNK)-specific MKP, during embryonic and imaginal disc development. We
demonstrate that Puc is a key anti-apoptotic factor that prevents apoptosis in
epithelial cells by restraining basal JNK signaling. Furthermore, we
demonstrate that JNK signaling plays an important role in
-irradiation-induced apoptosis, and examine how JNK signaling fits into
the circuitry regulating this process. Radiation upregulates both JNK activity
and puc expression in a p53-dependent manner, and apoptosis induced
by loss of Puc can be suppressed by p53 inactivation. JNK signaling acts
upstream of both Reaper and effector caspases. Finally, we demonstrate that
JNK signaling directs normal developmentally regulated apoptotic events.
However, if cell death is prevented, JNK activation can trigger tissue
overgrowth. Thus, MKPs are key regulators of the delicate balance between
proliferation, differentiation and apoptosis during development.
Key words: Apoptosis, JNK, Phosphatase, Drosophila
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