beta-transducin repeat containing E3 ubiquitin protein ligase or F-box/WD repeat-containing protein 1A (BTRC/FBXW1A) : Time behavioural study of 3rd order combinations in WNT3A stimulated HEK 293 cells

β TrCP (BTRC/FBXW1A) encodes a member of the F-box protein family, characterized by an approximately 40 residue structural motif, the F-box. The F-box proteins form one of the four subunits of ubiquitin protein ligase complex called Skp1-Cul1-F-box (SCF) protein, which often, but not always, recognize substrates in a phosphorylation-dependent manner. BTRC associates with phosphorylated β-catenin destruction motifs, probably functioning in multiple transcriptional programs by regulating the WNT pathways. Gujral and MacBeath [1] provides a quantitative, and dynamic study of WNT3A-mediated stimulation of HEK 293 cells, where they record time based expression profiles of several response genes which correlated significantly with proliferation and migration. By monitoring the dynamics of gene expression using self-organizing maps, they identified clusters of genes that exhibit similar expression dynamics and uncovered previously unrecognized positive and negative feedback loops. However, their study depicts/uses singular measurements of individual gene expression at different time snapshots/points to infer the system wide analysis of the pathway. At any particular time point, it is often the case that genes are working synergistically in combinations, even though their expression measurements are singular in nature. Here, I • enumerate and rank all 2415 BTRC related 3rd order combinations in a forest of 71C3 combinations using four different sensitivity methods; • show the conserved rankings for BTRC-X-X combinations, which point to existence of biological synergy of some of these combinations across the different sensitivity methods; and • study the behaviour of some of these combinations related to WNT3A response genes that are ranked by the machine learning search engine (Sinha [2]) in time. Patterns of combinations emerge, some of which have been tested in wet lab, while others require further wet lab analysis.