Page 19 - G. Cell differentiation. division. and death

BACKGROUND & AIM

Beclin1 is a key protein involved in mediating autophagy. When beclin1 is activated due to metabolic stress, it dissociates from the beclin1-bcl-2
heterodimer, forming beclin1 monomer. Subsequently, the beclin1 monomer forms the PI3K complex by interacting with Vps34, Vps15, and Atg14 to
induce autophagy. In this study, we identified another function of beclin1, and found that it is autophagy independent.
Necroptosis is a type of programmed cell death and, TNF-α-induced necroptosis is the most studied pathway of necroptosis. In TNF-α-induced
necroptosis, RIPK1 is activated by autophosphorylation. Phospho-RIPK1 subsequently phosphorylates RIPK3, and activated phoshpo-RIPK3 in turn
phosphorylates MLKL. The complex composed of RIPK1, RIPK3, and MLKL is called the necrosome, and is a key complex involved in necroptosis.
Phosphorylated MLKL forms an oligomer and translocates into the plasma membrane. MLKL oligomer in the plasma membrane causes membrane
rupture. Moreover, upon necrosome formation, beclin1 is recruited into the necrosome and it interacts with MLKL via a coiled-coil domain. Due to this
interaction, beclin1 in the necrosome inhibits MLKL oligomerization and consequently, necroptosis is suppressed.
RESULTS & METHODS

CONCLUSION REFERENCES ACKNOWLEDGEMENTS

• Beclin 1 suppresses TNF-induced • Seo J, Kim MW, Bae KH, Lee SC, Song J, Lee EW. The roles of This research was supported by a grant from the National
necroptosis in autophagy- ubiquitination in extrinsic cell death pathways and its Research Foundation of Korea (NRF) funded by the Ministry of
independent manner. implications for therapeutics. Biochem Pharmacol. Science, ICT and Future Planning This work was supported in part
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• Beclin 1 is incorporated into the • Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, et al. by Brain Korea 21 (BK21) PLUS program.
necrosome complex in necroptotic Phosphorylation-driven assembly of the RIP1-RIP3 complex
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• Beclin 1 interacts with p-MLKL and
inhibits MLKL oligomerization. • He S, Liang Y, Shao F, Wang X. Toll-like receptors activate Department of Biochemistry, College of Life science and Biotechnology, Yonsei
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Sung, Jaewhan Song (jso678@Yonsei.ac.kr)
for interaction with MLKL and
inhibition of MLKL oligomerization • He S, Wang L, Miao L, Wang T, Du F, Zhao L, et al. Receptor Environmental Disease Research Center, Korea Research Institute of Bioscience
interacting protein kinase-3 determines cellular necrotic and Biotechnology(KRIBB), Daejeon, Korea : Jinho Seo
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