Evidence for a growth-stabilizing regulatory feedback mechanism between Myc and Yorkie, the Drosophila homolog of Yap

Dev Cell. 2010 Oct 19;19(4):507-20. doi: 10.1016/j.devcel.2010.09.009.

Abstract

An understanding of how animal size is controlled requires knowledge of how positive and negative growth regulatory signals are balanced and integrated within cells. Here we demonstrate that the activities of the conserved growth-promoting transcription factor Myc and the tumor-suppressing Hippo pathway are codependent during growth of Drosophila imaginal discs. We find that Yorkie (Yki), the Drosophila homolog of the Hippo pathway transducer, Yap, regulates the transcription of Myc, and that Myc functions as a critical cellular growth effector of the pathway. We demonstrate that in turn, Myc regulates the expression of Yki as a function of its own cellular level, such that high levels of Myc repress Yki expression through both transcriptional and posttranscriptional mechanisms. We propose that the codependent regulatory relationship functionally coordinates the cellular activities of Yki and Myc and provides a mechanism of growth control that regulates organ size and has broad implications for cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins / chemistry*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / growth & development*
  • Drosophila melanogaster / metabolism*
  • Feedback, Physiological*
  • Gene Expression Regulation, Developmental
  • Genetic Loci / genetics
  • Homeostasis
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Models, Biological
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Sequence Homology, Amino Acid*
  • Signal Transduction
  • Trans-Activators / chemistry*
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc
  • Trans-Activators
  • Transcription Factors
  • Yki protein, Drosophila
  • sd protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • hpo protein, Drosophila