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Cell Commun Signal. 2018 Aug 15;16(1):46. doi: 10.1186/s12964-018-0256-8.

Systems level expression correlation of Ras GTPase regulators.

Author information

1
Institute of Pathology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.
2
Integrative Research Institute Life Sciences, Humboldt Universität Berlin, 10115, Berlin, Germany.
3
Centre for Genomic Regulation (CRG), Systems Biology Programme. The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain. christina.kiel@ucd.ie.
4
Present address: Systems Biology Ireland & Charles Institute of Dermatology & School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland. christina.kiel@ucd.ie.
5
Centre for Genomic Regulation (CRG), Systems Biology Programme. The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain.
6
Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.
7
Centre for Genomic Regulation (CRG), Systems Biology Programme. The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain. luis.serrano@crg.es.
8
Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain. luis.serrano@crg.es.
9
Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23, 08010, Barcelona, Spain. luis.serrano@crg.es.

Abstract

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.

KEYWORDS:

GTPase activating proteins; Gene expression network; Guanine nucleotide exchange factors; Ras small GTPases; Tissue expression

PMID:
30111366
PMCID:
PMC6094892
DOI:
10.1186/s12964-018-0256-8
[Indexed for MEDLINE]
Free PMC Article

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