最先端研究セミナー

招聘者： 川端 剛（長崎大学 原爆後障害医療研究所 准教授）

演題：Nucleolar starvation stress signaling and autophagy induction

日時：2026年7月1日（水）　12：00-13：00

開催場所：発生医学研究所1階　カンファレンス室　On site + Zoom

※ZOOMミーティングのURLはMoodleの「S-HIGO最先端研究セミナーA、B」にてご確認ください。

https://md.kumamoto-u.ac.jp/course/view.php?id=136783

Abstract：

Autophagy maintains cellular homeostasis through lysosomal degradation of cytoplasmic components, yet the signaling mechanisms coupling nuclear stress to autophagosome biogenesis remain unclear. Here, we demonstrate that ATR kinase, canonically known as a replication stress sensor, regulates starvation-induced canonical autophagy. ATR inhibition and genetic reduction suppressed autophagic flux and autophagosome formation. Phosphoproteomic screening of membrane-enriched fractions combined with an siRNA functional screen identified a nucleolar scaffold protein as an ATR substrate required for autophagosome biogenesis. Mechanistically, loss of this nucleolar factor caused hyperphosphorylation of the autophagy transcription factor TFEB and reduced its nuclear translocation in an ATR-dependent manner. These findings define an ATR–nucleolus–TFEB signaling axis that connects nucleolar stress sensing to activation of autophagy, revealing a non-canonical role for ATR as an integrator of metabolic stress and cellular quality control.

担当分野：損傷修復　立石（6605）