@article{49fff4499ca34c9b99e4480eb11879cb,
title = "Yorkie Growth-Promoting Activity Is Limited by Atg1-Mediated Phosphorylation",
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{\textquoteright}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.",
keywords = "Acinus, autophagy, growth control, scalloped",
author = "Tyra, {Lauren K.} and Nilay Nandi and Charles Tracy and Helmut Kr{\"a}mer",
note = "Funding Information: We thank Drs. Dean Smith, Jon Terman, and Duojia Pan for helpful comments on the manuscript and members of the Kr{\"a}mer lab for discussion and technical assistance. We thank Drs. Ken Irvine, Thomas Neufeld, Jin Jiang, Duojia Pan, the Vienna Drosophila Resource Center, and the Bloomington Drosophila Stock Center ( NIH P40OD018537 ) for flies; Drs. Duojia Pan, Iswar Hariharan, Dean Smith, and the Developmental Studies Hybridoma Bank at the University of Iowa for antibodies; and the Molecular and Cellular Imaging Facility at UT Southwestern Medical Center ( NIH S10 OD020103-01 ) for help with electron microscopy. This work was funded by NIH grants EY010199 and GM120196 to H.K. and NSF Graduate Research Fellowship ( 4900835401-36068 ) to L.K.T. Funding Information: We thank Drs. Dean Smith, Jon Terman, and Duojia Pan for helpful comments on the manuscript and members of the Kr?mer lab for discussion and technical assistance. We thank Drs. Ken Irvine, Thomas Neufeld, Jin Jiang, Duojia Pan, the Vienna Drosophila Resource Center, and the Bloomington Drosophila Stock Center (NIH P40OD018537) for flies; Drs. Duojia Pan, Iswar Hariharan, Dean Smith, and the Developmental Studies Hybridoma Bank at the University of Iowa for antibodies; and the Molecular and Cellular Imaging Facility at UT Southwestern Medical Center (NIH S10 OD020103-01) for help with electron microscopy. This work was funded by NIH grants EY010199 and GM120196 to H.K. and NSF Graduate Research Fellowship (4900835401-36068) to L.K.T. Conceptualization, L.K.T. N.N. and H.K.; Methodology, L.K.T. N.N. C.T. and H.K.; Investigation, L.K.T. N.N. C.T. and H.K.; Writing ? Original Draft, L.K.T.; Writing ? Review & Edit, L.K.T. N.N. C.T. and H.K.; Funding Acquisition, L.K.T. and H.K.; and Supervision, H.K. The authors declare no competing interests.",
year = "2020",
month = mar,
day = "9",
doi = "10.1016/j.devcel.2020.01.011",
language = "English (US)",
volume = "52",
pages = "605--616.e7",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "5",
}