Genome-wide survey of protein kinases required for cell cycle progression

Nature. 2004 Dec 23;432(7020):980-7. doi: 10.1038/nature03160.

Abstract

Cycles of protein phosphorylation are fundamental in regulating the progression of the eukaryotic cell through its division cycle. Here we test the complement of Drosophila protein kinases (kinome) for cell cycle functions after gene silencing by RNA-mediated interference. We observed cell cycle dysfunction upon downregulation of 80 out of 228 protein kinases, including most kinases that are known to regulate the division cycle. We find new enzymes with cell cycle functions; some of these have family members already known to phosphorylate microtubules, actin or their associated proteins. Additionally, depletion of several signalling kinases leads to specific mitotic aberrations, suggesting novel roles for familiar enzymes. The survey reveals the inter-digitation of systems that monitor cellular physiology, cell size, cellular stress and signalling processes with the basic cell cycle regulatory machinery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Cycle / physiology*
  • Cell Proliferation
  • Cytokinesis
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / enzymology*
  • Drosophila melanogaster / genetics
  • G2 Phase
  • Genome*
  • Genomics
  • Mitosis / physiology
  • Mutation / genetics
  • Nutritional Status
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • RNA Interference
  • S Phase
  • Signal Transduction
  • Spindle Apparatus / physiology
  • Stress, Physiological / genetics
  • Stress, Physiological / physiopathology

Substances

  • Drosophila Proteins
  • Protein Kinases
  • LKB1 protein, Drosophila