JNK pathway mediates apoptotic cell death induced by tumor suppressor LKB1 in Drosophila

Although recent progresses have unveiled the diverse in vivo functions of LKB1, detailed molecular mechanisms governing these processes still remain enigmatic. Here, we showed that Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis, without affecting cell size and cell cycle progression. Through genetic screening for LKB1 modifiers, we discovered the JNK pathway as a novel component of LKB1 signaling; the JNK pathway was activated by LKB1 and mediated the LKB1-dependent apoptosis. Consistently, LKB1-null mutant was defective in embryonic apoptosis and displayed a drastic hyperplasia in the central nervous system; these phenotypes were fully rescued by ectopic JNK activation as well as wild-type LKB1 expression. Furthermore, inhibition of LKB1 resulted in epithelial morphogenesis failure, which was associated with a decrease in JNK activity. Collectively, our studies unprecedentedly elucidate JNK as the downstream mediator of the LKB1-dependent apoptosis, and provide a new paradigm for understanding the diverse LKB1 functions in vivo.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2006-07
Language
ENG
Keywords

PEUTZ-JEGHERS-SYNDROME; TUBEROUS SCLEROSIS COMPLEX; PROTEIN-KINASE; SIGNAL-TRANSDUCTION; INCREASED RISK; GROWTH ARREST; GENE; CANCER; MORPHOGENESIS; PROLIFERATION

Citation

CELL DEATH AND DIFFERENTIATION, v.13, no.7, pp.1110 - 1122

ISSN
1350-9047
DOI
10.1038/sj.cdd.4401790
URI
http://hdl.handle.net/10203/5620
Appears in Collection
BS-Journal Papers(저널논문)
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