Genome-scale functional profiling of the mammalian AP-1 signaling pathway

Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12153-8. doi: 10.1073/pnas.1934839100. Epub 2003 Sep 26.


Large-scale functional genomics approaches are fundamental to the characterization of mammalian transcriptomes annotated by genome sequencing projects. Although current high-throughput strategies systematically survey either transcriptional or biochemical networks, analogous genome-scale investigations that analyze gene function in mammalian cells have yet to be fully realized. Through transient overexpression analysis, we describe the parallel interrogation of approximately 20,000 sequence annotated genes in cancer-related signaling pathways. For experimental validation of these genome data, we apply an integrative strategy to characterize previously unreported effectors of activator protein-1 (AP-1) mediated growth and mitogenic response pathways. These studies identify the ADP-ribosylation factor GTPase-activating protein Centaurin alpha1 and a Tudor domain-containing hypothetical protein as putative AP-1 regulatory oncogenes. These results provide insight into the composition of the AP-1 signaling machinery and validate this approach as a tractable platform for genome-wide functional analysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Chickens
  • DNA, Complementary / genetics
  • Gene Expression Profiling
  • Genome, Human
  • Genomics
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Signal Transduction*
  • Transcription Factor AP-1 / genetics*
  • Transcription Factor AP-1 / metabolism*
  • Transfection


  • DNA, Complementary
  • Transcription Factor AP-1