ArticleBMC systems biology2008
A simple principle concerning the robustness of protein complex activity to changes in gene expression.
Article in BMC systems biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed.
- Evolutionary causes and consequences of gene duplication.Nature reviews. Genetics · 2026Review
- Non-canonical subunit functions in multiprotein complexes: insights from the Mediator complex.Biochemical Society transactions · 2026Review
- Comparative modeling reveals the molecular determinants of aneuploidy fitness cost in a wild yeast model.Cell genomics · 2024Article
- Comparative modeling reveals the molecular determinants of aneuploidy fitness cost in a wild yeast model.bioRxiv : the preprint server for biology · 2024Article
- Retention of duplicated genes in evolution.Trends in genetics : TIG · 2022Review
- Expression attenuation as a mechanism of robustness against gene duplication.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Link clustering explains non-central and contextually essential genes in protein interaction networks.Scientific reports · 2019Article
- The role of protein complexes in human genetic disease.Protein science : a publication of the Protein Society · 2019Review
- Destabilization of AETFC through C/EBPα-mediated repression of LYL1 contributes to t(8;21) leukemic cell differentiation.Leukemia · 2019Article
- Article
- The OsPS1-F gene regulates growth and development in rice by modulating photosynthetic electron transport rate.Plant cell reports · 2018Article
- Endocytic recycling protein EHD1 regulates primary cilia morphogenesis and SHH signaling during neural tube development.Scientific reports · 2016Article
- Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response pathways.NPJ systems biology and applications · 2016Article
- Concerted copy number variation balances ribosomal DNA dosage in human and mouse genomes.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Evolutionary diversification of the multimeric states of proteins.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- All or nothing: protein complexes flip essentiality between distantly related eukaryotes.Genome biology and evolution · 2013Article
- Evolutionary rate heterogeneity of core and attachment proteins in yeast protein complexes.Genome biology and evolution · 2013Article
- The evolution of multimeric protein assemblages.Molecular biology and evolution · 2012Article
- Integrated genome-scale prediction of detrimental mutations in transcription networks.PLoS genetics · 2011Article
- The repatterning of eukaryotic genomes by random genetic drift.Annual review of genomics and human genetics · 2011Review
Corrections and comments
- Commented on by
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe 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.
resultsIn 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.
conclusionWe 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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.