演題：Nucleolar starvation stress signaling and autophagy induction

演者：Tsuyoshi Kawabata　(川端剛)

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.

Reference

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