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SIRT1 and AROS suppress doxorubicin-induced apoptosis via inhibition of GSK3β activity in neuroblastoma cells

Animal Cells and Systems 2020년 24권 1호 p.53 ~ 59
김정우, 양지혜, 김은주,
소속 상세정보
김정우 ( Kim Jeong-Woo ) - Dankook University Department of Molecular Biology
양지혜 ( Yang Ji-Hye ) - Dankook University Department of Molecular Biology
김은주 ( Kim Eun-Joo ) - Dankook University Department of Molecular Biology

Abstract


SIRT1, the best-characterized member of the sirtuin family of deacetylases, is involved in cancer, apoptosis, inflammation, and metabolism. Active regulator of SIRT1 (AROS) was the first identified direct regulator of SIRT1. An increasing number of reports have indicated that SIRT1 plays an important role in controlling brain tumors. Here, we demonstrated that depletion of SIRT1 and AROS increases doxorubicin-mediated apoptosis in human neuroblastoma SH-SY5Y cells. Glycogen synthase kinase 3β (GSK3β) promoted doxorubicin-mediated apoptosis, but this effect was abolished by overexpression of SIRT1 and AROS. Interestingly, SIRT1 and AROS interacted with GSK3β and increased inhibitory phosphorylation of GSK3β on Ser9. Finally, we determined that AROS cooperates with SIRT1 to suppress GSK3β acetylation. Taken together, our results suggest that SIRT1 and AROS inhibit GSK3β activity and provide additional insight into drug resistance in the treatment of neuroblastoma.

키워드

SIRT1; GSK3β; apoptosis; neuroblastoma

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