Drosophila Low Temperature Viability Protein 1 (LTV1) Is Required for Ribosome Biogenesis and Cell Growth Downstream of Drosophila Myc (dMyc)

J Biol Chem. 2015 May 22;290(21):13591-604. doi: 10.1074/jbc.M114.607036. Epub 2015 Apr 9.

Abstract

During animal development, various signaling pathways converge to regulate cell growth. In this study, we identified LTV1 as a novel cell growth regulator in Drosophila. LTV1 mutant larvae exhibited developmental delays and lethality at the second larval stage. Using biochemical studies, we discovered that LTV1 interacted with ribosomal protein S3 and co-purified with free 40S ribosome subunits. We further demonstrated that LTV1 is crucial for ribosome biogenesis through 40S ribosome subunit synthesis and preribosomal RNA processing, suggesting that LTV1 is required for cell growth by regulating protein synthesis. We also demonstrated that Drosophila Myc (dMyc) directly regulates LTV1 transcription and requires LTV1 to stimulate ribosome biogenesis. Importantly, the loss of LTV1 blocked the cell growth and endoreplication induced by dMyc. Combined, these results suggest that LTV1 is a key downstream factor of dMyc-induced cell growth by properly maintaining ribosome biogenesis.

Keywords: Drosophila; LTV1; Myc (c-Myc); cell growth; ribosomal RNA processing (rRNA processing); ribosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified / genetics
  • Animals, Genetically Modified / growth & development
  • Animals, Genetically Modified / metabolism*
  • Blotting, Northern
  • Cell Proliferation
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism*
  • Immunoenzyme Techniques
  • Microscopy, Electron
  • Protein Biosynthesis*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribosomes / genetics
  • Ribosomes / metabolism*
  • Temperature

Substances

  • Drosophila Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger