Yorkie Growth-Promoting Activity Is Limited by Atg1-Mediated Phosphorylation

Lauren K. Tyra, Nilay Nandi, Charles Tracy, Helmut Krämer

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The expression of multiple growth-promoting genes is coordinated by the transcriptional co-activator Yorkie with its major regulatory input provided by the Hippo-Warts kinase cascade. Here, we identify Atg1/ULK1-mediated phosphorylation of Yorkie as an additional inhibitory input independent of the Hippo-Warts pathway. Two serine residues in Yorkie, S74 and S97, are Atg1/ULK1 consensus target sites and are phosphorylated by ULK1 in vitro, thereby preventing its binding to Scalloped. In vivo, gain of function of Atg1, or its activator Acinus, caused elevated Yorkie phosphorylation and inhibited Yorkie's growth-promoting activity. Loss of function of Atg1 or Acinus raised expression of Yorkie target genes and increased tissue size. Unlike Atg1’s role in autophagy, Atg1-mediated phosphorylation of Yorkie does not require Atg13. Atg1 is activated by starvation and other cellular stressors and therefore can impose temporary stress-induced constraints on the growth-promoting gene networks under the control of Hippo-Yorkie signaling.

Original languageEnglish (US)
Pages (from-to)605-616.e7
JournalDevelopmental cell
Volume52
Issue number5
DOIs
StatePublished - Mar 9 2020

Keywords

  • Acinus
  • autophagy
  • growth control
  • scalloped

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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