A protein interaction atlas for the nuclear receptors: properties and quality of a hub-based dimerisation network.
BACKGROUND
The nuclear receptors are a large family of eukaryotic transcription factors that constitute major pharmacological targets. They exert their combinatorial control through homotypic heterodimerisation. Elucidation of this dimerisation network is vital in order to understand the complex dynamics and potential cross-talk involved.


RESULTS
Phylogeny, protein-protein interactions, protein-DNA interactions and gene expression data have been integrated to provide a comprehensive and up-to-date description of the topology and properties of the nuclear receptor interaction network in humans. We discriminate between DNA-binding and non-DNA-binding dimers, and provide a comprehensive interaction map, that identifies potential cross-talk between the various pathways of nuclear receptors.


CONCLUSIONS
We infer that the topology of this network is hub-based, and much more connected than previously thought. The hub-based topology of the network and the wide tissue expression pattern of NRs create a highly competitive environment for the common heterodimerising partners. Furthermore, a significant number of negative feedback loops is present, with the hub protein SHP [NR0B2] playing a major role. We also compare the evolution, topology and properties of the nuclear receptor network with the hub-based dimerisation network of the bHLH transcription factors in order to identify both unique themes and ubiquitous properties in gene regulation. In terms of methodology, we conclude that such a comprehensive picture can only be assembled by semi-automated text-mining, manual curation and integration of data from various sources.
Amoutzias
Gregory D
GD
Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK. grigoris.amoutzias@psb.ugent.be
Pichler
Elgar E
EE
Mian
Nina
N
De Graaf
David
D
Imsiridou
Anastasia
A
Robinson-Rechavi
Marc
M
Bornberg-Bauer
Erich
E
Robertson
David L
DL
Oliver
Stephen G
SG
D000818:Animals; D004247:DNA / Q000378:metabolism; D030562:Databases, Protein; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D051379:Mice; D010802:Phylogeny; D011485:Protein Binding; D025941:Protein Interaction Mapping; D018160:Receptors, Cytoplasmic and Nuclear / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000145:classification / Q000235:genetics / Q000378:metabolism*
D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D004247:DNA