Systems level expression correlation of Ras GTPase regulators

Background: Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be...

Descripción completa

Detalles Bibliográficos
Autores: Unal, E. Besray, Kiel, Christina, Benisty, Hannah, 1986-, Campbell, Andrew, Pickering, Karen, Blüthgen, Nils, Sansom, Owen J., Serrano Pubull, Luis, 1982-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/42587
Acceso en línea:http://hdl.handle.net/10230/42587
http://dx.doi.org/10.1186/s12964-018-0256-8
Access Level:acceso abierto
Palabra clave:Ras small GTPases
Tissue expression
Gene expression network
GTPase activating proteins
Guanine nucleotide exchange factors
Descripción
Sumario:Background: Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. Methods: We performed Spearman’s rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed. Results: We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals. Conclusions: Our results are relevant for critical considerations of knock out experiments, where functionally related homologs may compensate for the down regulation of a protein.