MLKL-매개 내막수송 결함에 의한 TRAIL-유도 암세포 사멸신호 증가에 대한 연구

Alternative Title
Park, Se Yeon
Alternative Author(s)
Park, Se Yeon
일반대학원 의생명과학과
The Graduate School, Ajou University
Publication Year
Alternative Abstract
Mixed Lineage Kinase Domain-like (MLKL) is the essential molecule of programmed necrotic cell death, Necroptosis. To induce necroptosis, MLKL is phosphorylated by upstream partner, Receptor Interacting Protein Kinase-3 (RIPK3 or RIP3) and then translocate cellular membrane to disrupt membrane integrity. Recent data suggests that function of MLKL in RIP3-indendent manner in the effective generation of intraluminal and extracellular vesicles as well as in myelin sheath breakdown to promotes sciatic nerve regeneration. In this study, we investigated that whether MLKL play a role in link between TRAIL receptor endocytosis and apoptosis. Depletion of MLKL enhances TRAIL-induced cell death in various cancer cell lines and enhancement of cell death is RIP3-independent manner. TRAIL-induced cytotoxic signals are further increased by preventing endocytosis and MLKL depletion facilitates degradation of TRAIL-DR5. TRAIL-induced intracellular downstream signals were prolonged by depletion of MLKL and then prolonged cytotoxic signals promote cell death. Our data indicate that defect of the intracellular trafficking of TRAIL-DR5 by depletion of MLKL enhances cancer cell death. Based on our findings, it is tempting to speculate that to promote death receptor signals, it may effective to reduced MLKL expression and to prevent survival receptor signal, upregulated MLKL expression contribute to abolish the intracellular signal through the MLKL-dependent extracellular vesicles secretion. Although the processes that regulate these pathways require further elucidation for detail molecular mechanisms, both ways will be the potent therapeutic strategies to target cancer.

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Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
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