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A Protocol for Genetic Induction and Visualization of Benign and Invasive Tumors in Cephalic Complexes of Drosophila melanogaster
Published on: September 11, 2013
JNK pathway mediates apoptotic cell death induced by tumor suppressor LKB1 in Drosophila
1National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373-1 Kusong-dong, Yusong, Taejon, Korea.
Abstract:
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.
Insights
Liver kinase B1 (LKB1) regulates organ growth through apoptosis, with the JNK pathway mediating this process. This study reveals JNK as a key downstream mediator of LKB1 signaling in vivo.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Signaling
Background:
- Liver kinase B1 (LKB1) is known to have diverse in vivo functions, but the underlying molecular mechanisms are not fully understood.
- LKB1's role in regulating organ growth and its precise signaling pathways require further elucidation.
Purpose of the Study:
- To investigate the molecular mechanisms by which LKB1 regulates organ growth in Drosophila.
- To identify novel components and pathways involved in LKB1 signaling.
- To elucidate the role of the JNK pathway in LKB1-mediated apoptosis and organ development.
Main Methods:
- Genetic screening for modifiers of LKB1 in Drosophila.
- Analysis of LKB1 function in organ growth, apoptosis, cell size, and cell cycle progression.
- Investigating the activation and mediation of apoptosis by the JNK pathway in relation to LKB1.
Main Results:
- Drosophila LKB1 negatively regulates organ growth via caspase-dependent apoptosis, independent of cell size and cell cycle.
- The JNK pathway is identified as a novel component of LKB1 signaling, activated by LKB1 and mediating apoptosis.
- LKB1-null mutants show defective embryonic apoptosis and central nervous system hyperplasia, rescued by JNK activation or LKB1 expression.
- LKB1 inhibition leads to epithelial morphogenesis failure associated with decreased JNK activity.
Conclusions:
- The JNK pathway is a crucial downstream mediator of LKB1-dependent apoptosis.
- This study provides a new framework for understanding LKB1's diverse in vivo functions.
- LKB1 signaling, through JNK, plays a critical role in regulating organ growth and development.
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