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Determining signalling nodes for apoptosis by a genetic high-throughput screen

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Title: Determining signalling nodes for apoptosis by a genetic high-throughput screen
Authors: Lin, B
Huntley, D
AbuAli, G
Langley, SR
Sindelar, G
Petretto, E
Butcher, S
Grimm, S
Item Type: Journal Article
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 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/Significance: 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.
Issue Date: 22-Sep-2011
Date of Acceptance: 25-Aug-2011
URI: http://hdl.handle.net/10044/1/57208
DOI: https://dx.doi.org/10.1371/journal.pone.0025023
ISSN: 1932-6203
Publisher: Public Library of Science (PLoS)
Journal / Book Title: PLoS ONE
Volume: 6
Issue: 9
Copyright Statement: © 2011 Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited (https://creativecommons.org/licenses/by/3.0/).
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
PERMEABILITY TRANSITION-PORE
CELL-DEATH
REGULATES APOPTOSIS
BH3-ONLY PROTEIN
PLASMID DNA
CANCER
IDENTIFICATION
INDUCTION
COMPONENT
BIOLOGY
Animals
Apoptosis
Computational Biology
DNA, Complementary
Enzyme-Linked Immunosorbent Assay
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genomics
Green Fluorescent Proteins
HEK293 Cells
Humans
Mice
Models, Genetic
Oligonucleotide Array Sequence Analysis
Robotics
Signal Transduction
Subcellular Fractions
MD Multidisciplinary
General Science & Technology
Publication Status: Published
Article Number: ARTN e25023
Appears in Collections:Division of Surgery
Clinical Sciences
Molecular Sciences
Faculty of Medicine
Faculty of Natural Sciences



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