'Edgetic' perturbation of a C. elegans BCL2 ortholog.
Genes and gene products do not function in isolation but within highly interconnected 'interactome' networks, modeled as graphs of nodes and edges representing macromolecules and interactions between them, respectively. We propose to investigate genotype-phenotype associations by methodical use of alleles that lack single interactions, while retaining all others, in contrast to genetic approaches designed to eliminate gene products completely. We describe an integrated strategy based on the reverse yeast two-hybrid system to isolate and characterize such edge-specific, or 'edgetic', alleles. We established a proof of concept with CED-9, a Caenorhabditis elegans BCL2 ortholog. Using ced-9 edgetic alleles, we uncovered a new potential functional link between apoptosis and a centrosomal protein. This approach is amenable to higher throughput and is particularly applicable to interactome network analysis in organisms for which transgenesis is straightforward.
Dreze
Matija
M
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Charloteaux
Benoit
B
Milstein
Stuart
S
Vidalain
Pierre-Olivier
PO
Yildirim
Muhammed A
MA
Zhong
Quan
Q
Svrzikapa
Nenad
N
Romero
Viviana
V
Laloux
Géraldine
G
Brasseur
Robert
R
Vandenhaute
Jean
J
Boxem
Mike
M
Cusick
Michael E
ME
Hill
David E
DE
Vidal
Marc
M
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000235:genetics; D017238:Genes, Helminth; D005838:Genotype; D008958:Models, Molecular; D010641:Phenotype; D025941:Protein Interaction Mapping / Q000379:methods*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012097:Repressor Proteins / Q000502:physiology; D020798:Two-Hybrid System Techniques
D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C089224:Ced-4 protein, C elegans; C087233:Ced-9 protein, C elegans; C112486:EGL-1 protein, C elegans; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins