title: A simple principle concerning the robustness of protein complex activity to changes in gene expression.
abstract: BACKGROUND
  The functions of a eukaryotic cell are largely performed by multi-subunit protein complexes that act as molecular machines or information processing modules in cellular networks. An important problem in systems biology is to understand how, in general, these molecular machines respond to perturbations.
  
  
  RESULTS
  In yeast, genes that inhibit growth when their expression is reduced are strongly enriched amongst the subunits of multi-subunit protein complexes. This applies to both the core and peripheral subunits of protein complexes, and the subunits of each complex normally have the same loss-of-function phenotypes. In contrast, genes that inhibit growth when their expression is increased are not enriched amongst the core or peripheral subunits of protein complexes, and the behaviour of one subunit of a complex is not predictive for the other subunits with respect to over-expression phenotypes.
  
  
  CONCLUSIONS
  We propose the principle that the overall activity of a protein complex is in general robust to an increase, but not to a decrease in the expression of its subunits. This means that whereas phenotypes resulting from a decrease in gene expression can be predicted because they cluster on networks of protein complexes, over-expression phenotypes cannot be predicted in this way. We discuss the implications of these findings for understanding how cells are regulated, how they evolve, and how genetic perturbations connect to disease in humans.
authors.affiliation: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG), UPF, Dr, Aiguader 88, Barcelona 08003, Spain. jennifer.semple@crg.es
authors.forename: Jennifer I
authors.initials: JI
authors.lastname: Semple
authors.forename: Tanya
authors.initials: T
authors.lastname: Vavouri
authors.forename: Ben
authors.initials: B
authors.lastname: Lehner
mesh_terms: D015536:Down-Regulation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D016681:Genome, Fungal / Q000502:physiology; D006128:Growth / Q000235:genetics; D046912:Multiprotein Complexes / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D013269:Stochastic Processes; D013329:Structure-Activity Relationship; D015854:Up-Regulation; D015003:Yeasts / Q000235:genetics / Q000254:growth & development / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D046912:Multiprotein Complexes