02099nas a2200181   4500008004100000022001400041245008800055210006900143260010300212300001100315490000800326520137100334100003001705700002101735700002101756700002301777856011701800       2016                        eng d  a0021-925800aIdentification of unintuitive features of sumoylation through mathematical modeling0 aIdentification of unintuitive features of sumoylation through ma  a9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USAbAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INCcAPR  a9458-+0 v2913 a<p>Sumoylation is a multistep, multienzymatic post-translational modification in which a small ubiquitin-like modifier protein (SUMO) is attached to the target. We present the first mathematical model for sumoylation including enzyme mechanism details such as autosumoylation of E2 and multifunctional nature of SENP. Simulations and analysis reveal three nonobvious properties for the long term response, modeled as an open system: (i) the steady state sumoylation level is robust to variation in several enzyme properties; (ii) even when autosumoylation of E2 results in equal or higher activity, the target sumoylation levels are lower; and (iii) there is an optimal SENP concentration at which steady state target sumoylation level is maximum. These results are qualitatively different for a short term response modeled as a closed system, where e.g. sumoylation always decreases with increasing SENP levels. Simulations with multiple targets suggest that the available SUMO is limiting, indicating a possible explanation for the experimentally observed low fractional sumoylation. We predict qualitative differences in system responses at short post-translational and longer transcriptional time scales. We thus use this mechanism-based model to explain system properties and generate testable hypotheses for existence and mechanism of unexpected responses.</p>1 aPuntambekar, Shraddha, S.1 aNyayanit, Dimpal1 aSaxena, Priyanka1 aGadgil, Chetan, J.  uhttps://library.ncl.res.in/content/identification-unintuitive-features-sumoylation-through-mathematical-modeling