title: Identification of Unintuitive Features of Sumoylation through Mathematical Modeling.
abstract: 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.
authors: From the Chemical Engineering and Process Development Division, CSIR-National Chemical Laboratory, Pune-411008, and the Academy of Scientific and Innovative Research (AcSIR), CSIR-NCL Campus, Pune-411008, and.
authors: Shraddha S
authors: SS
authors: Puntambekar
authors: From the Chemical Engineering and Process Development Division, CSIR-National Chemical Laboratory, Pune-411008, and the Academy of Scientific and Innovative Research (AcSIR), CSIR-NCL Campus, Pune-411008, and.
authors: Dimpal
authors: D
authors: Nyayanit
authors: the Academy of Scientific and Innovative Research (AcSIR), CSIR-NCL Campus, Pune-411008, and the CSIR-Institute of Genomics and Integrative Biology, New Delhi 110020, India.
authors: Priyanka
authors: P
authors: Saxena
authors: From the Chemical Engineering and Process Development Division, CSIR-National Chemical Laboratory, Pune-411008, and the Academy of Scientific and Innovative Research (AcSIR), CSIR-NCL Campus, Pune-411008, and the CSIR-Institute of Genomics and Integrative Biology, New Delhi 110020, India cj.gadgil@ncl.res.in.
authors: Chetan J
authors: CJ
authors: Gadgil
mesh_terms: D000818:Animals; D006801:Humans; D008954:Models, Biological; D058207:Sumoylation / Q000502:physiology*
keywords: automodification; bifunctional enzyme; cyclic pathway; enzyme catalysis; enzyme kinetics; mathematical modeling; post-translational modification (PTM); sumoylation