determining signalling nodes for apoptosis by a genetic high-throughput screen确定信号节点细胞凋亡基因筛选.pdfVIP

Determining Signalling Nodes for Apoptosis by a Genetic High-Throughput Screen 1 2 1 3 1¤ 3,4 Bevan Lin , Derek Huntley , Ghada AbuAli , Sarah R. Langley , George Sindelar , Enrico Petretto , 2 1 Sarah Butcher , Stefan Grimm * 1 Division of Experimental Medicine, Imperial College London, London, United Kingdom, 2 Bioinformatics Support Service, Imperial College London, London, United Kingdom, 3 Medical Research Council-Clinical Sciences Centre, Imperial College London, London, United Kingdom, 4 Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom 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. Methodology/Principal Findings: 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 deter