'Edgetic' perturbation of a C. elegans BCL2 ortholog.

Alleles; Amino Acid Sequence; Animals; Binding Sites; Caenorhabditis elegans/genetics; Caenorhabditis elegans Proteins/genetics/physiology; Calcium-Binding Proteins/genetics; Genes, Helminth; Genotype; Models, Molecular; Phenotype; Protein Interaction Mapping/methods; Proto-Oncogene Proteins c-bcl-2/genetics; Repressor Proteins/physiology; Two-Hybrid System Techniques

Abstract :

[en] 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.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Dreze, Matija

Charloteaux, Benoît ; Université de Liège - ULiège > Gembloux Agro-Bio Tech

Milstein, Stuart

Vidalain, Pierre*-Olivier

Yildirim, Muhammed A

Zhong, Quan

Svrzikapa, Nenad

Romero, Viviana

Laloux, Geraldine

Brasseur, Robert ; Université de Liège - ULiège > Gembloux Agro-Bio Tech

More authors (5 more)

Language :

English

Title :

'Edgetic' perturbation of a C. elegans BCL2 ortholog.

Publication date :

2009

Journal title :

Nature Methods

ISSN :

1548-7091

eISSN :

1548-7105

Publisher :

Nature Publishing Group

Volume :

Issue :

Pages :

843-9

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 23 June 2010

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