Several members of the same team that studied cell type-specific nuclear pores asked this question in a new study published in Genome Biology [8]. First, they built a protein complex resource from several database sources, including CORUM and COMPLEAT, that was then filtered to contain 279 protein complexes that each contains at least five distinct proteins, making a total of 2048 unique proteins. They then selected two large-scale quantitative proteomic datasets. One described an analysis of 11 human cell lines [9] and the other an analysis of mouse embryonic fibroblasts (MEFs) that had been induced into pluripotent stem cells (iPSCs) [10]. These original articles [9, 10] are both well executed, and detailed, quantitative proteomic studies, but it is important to bear in mind that they cover only a small fraction of the total number of possible cellular states. The authors then mapped the 279 protein complexes onto these two quantitative proteomic datasets and found that 182 were detected in one or the other of the datasets, and of these 116 were observed in both. A sizable portion of protein complex members were differentially expressed in both datasets, leading to the description of stable or variable protein complexes.
Over half of the 182 protein complexes analyzed were variable. More specifically, 102 of the complexes analyzed were variable, and 80 were stable. Stable complexes included the ribosome, the proteasome, mitochondrial protein complexes, and the exosome. However, some variability was seen in the ribosome, consistent with emerging evidence regarding the functional importance of specialized ribosomes [5]. By contrast, variable complexes included those involved in mRNA transport, vesicle-mediated transport and chromatin remodeling. Specific examples of variable complexes include TREX, COPII, COPI, SWI/SNF (BAF) and NuRD. From the quantitative proteomics datasets analyzed on different human cell lines [9], and iPSCs from MEFs [10], the major variable complexes were epigenetic regulators and transport systems.
These observations raise questions concerning how these variable complexes are regulated. Certainly, detailed and focused studies on each of the complexes are warranted in the future, but here the authors searched for general principles. They focused on the induced pluripotency dataset in mouse because gene expression data were available. Fewer than half of the cases of variant changes were likely attributable to transcriptional regulation, where protein and transcript abundance changed in the same direction at the same point in time. Almost two-thirds of the cases appear to be regulation at the level of translation or protein turnover. An analysis of structures from the Protein Data Bank suggested that stable interactions have structural properties different to those of variable interactions. Specifically, the authors suggest that variable interfaces are less hydrophobic than stable interfaces and might be more accessible to regulatory events such as phosphorylation.