title: Determining signalling nodes for apoptosis by a genetic high-throughput screen.
abstract: BACKGROUND
  With the ever-increasing information emerging from the various sequencing and gene annotation projects, there is an urgent need to elucidate the cellular functions of the newly discovered genes. The genetically regulated cell suicide of apoptosis is especially suitable for such endeavours as it is governed by a vast number of factors.
  
  
  RESULTS
  We have set up a high-throughput screen in 96-well microtiter plates for genes that induce apoptosis upon their individual transfection into human cells. Upon screening approximately 100,000 cDNA clones we determined 74 genes that initiate this cellular suicide programme. A thorough bioinformatics analysis of these genes revealed that 91% are novel apoptosis regulators. Careful sequence analysis and functional annotation showed that the apoptosis factors exhibit a distinct functional distribution that distinguishes the cell death process from other signalling pathways. While only a minority of classic signal transducers were determined, a substantial number of the genes fall into the transporter- and enzyme-category. The apoptosis factors are distributed throughout all cellular organelles and many signalling circuits, but one distinct signalling pathway connects at least some of the isolated genes. Comparisons with microarray data suggest that several genes are dysregulated in specific types of cancers and degenerative diseases.
  
  
  CONCLUSIONS
  Many unknown genes for cell death were revealed through our screen, supporting the enormous complexity of cell death regulation. Our results will serve as a repository for other researchers working with genomics data related to apoptosis or for those seeking to reveal novel signalling pathways for cell suicide.
authors.affiliation: Division of Experimental Medicine, Imperial College London, London, United Kingdom.
authors.forename: Bevan
authors.initials: B
authors.lastname: Lin
authors.forename: Derek
authors.initials: D
authors.lastname: Huntley
authors.forename: Ghada
authors.initials: G
authors.lastname: Abuali
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Langley
authors.forename: George
authors.initials: G
authors.lastname: Sindelar
authors.forename: Enrico
authors.initials: E
authors.lastname: Petretto
authors.forename: Sarah
authors.initials: S
authors.lastname: Butcher
authors.forename: Stefan
authors.initials: S
authors.lastname: Grimm
mesh_terms: D000818:Animals; D017209:Apoptosis; D019295:Computational Biology / Q000379:methods; D018076:DNA, Complementary / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D012371:Robotics; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D049452:Green Fluorescent Proteins