SUMO1/sentrin/SMT3 specific peptidase 2 (SENP2/AXAM2) : Time behavioural study of 3rd order combinations in WNT3A stimulated HEK 293 cells

SENP2 is cysteine protease that belongs to the family of sentrin-specific protease, which come under the broader group of SUMO-specific isopeptidases and proteases. The ubiquitin-like SUMO (small ubiquitin-related modifier) system is a post-translational protein modification pathway in eukaryotes, where SUMOylation is a highly dynamic process and deconjugation (deSUMOylation) is catalyzed by a family of cysteine pro- teases, termed SUMO-specific proteases or SUMO isopeptidases. SENP2 processes newly synthesized SUMO1 into the conjugatable form and catalyze the deconjugation of SUMO1-containing species. 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 us- ing 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 syner- gistically in combinations, even though their expression measurements are singular in nature. Here, I • enumerate and rank all 2415 SENP2 related 3rd order combinations in a forest of 71C3 combinations using four different sensitivity methods; • show the con- served rankings for SENP2-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.