tailieunhanh - Báo cáo khoa học: A steady-state modeling approach to validate an in vivo mechanism of the GAL regulatory network in Saccharomyces cerevisiae

Cellular regulation is a result of complex interactions arising from DNA–protein and protein–protein binding, autoreg-ulation, and compartmentalization and shuttling of regula-tory proteins. Experiments in molecular biology have identified these mechanisms recruited by a regulatory used to complement the knowledge-base provided byin vitroexperimental methods. Interactions identified byin vitroexperiments can lead to the hypothesis of multiple candidate models explaining the in vivo mechanism. . | Eur. J. Biochem. 271 4064-4074 2004 FEBS 2004 doi A steady-state modeling approach to validate an in vivo mechanism of the GAL regulatory network in Saccharomyces cerevisiae Malkhey Verma1 Paike J. Bhat2 Sharad Bhartiya1 and K. V. Venkatesh1 2 1 Department of Chemical Engineering and 2School of Biosciences and Bioengineering Indian Institute of Technology Bombay Powai Mumbai India Cellular regulation is a result of complex interactions arising from DNA-protein and protein-protein binding autoregulation and compartmentalization and shuttling of regulatory proteins. Experiments in molecular biology have identified these mechanisms recruited by a regulatory network. Mathematical models may be used to complement the knowledge-base provided by in vitro experimental methods. Interactions identified by in vitro experiments can lead to the hypothesis of multiple candidate models explaining the in vivo mechanism. The equilibrium dissociation constants for the various interactions and the total component con centration constitute constraints on the candidate models. In this work we identify the most plausible in vivo network by comparing the output response to the experimental data. We demonstrate the methodology using the GAL system of Saccharomyces cerevisiae for which the steady-state analysis reveals that Gal3p neither dimerizes nor shuttles between the cytoplasm and the nucleus. Keywords Gal4p binding sites gene expression nucleo-cytoplasmic shuttling regulatory networks Saccharomyces cerevisiae. Intracellular regulatory networks are complex systems whose operation represents a highly coordinated orchestration connecting metabolic pathways signal transduction and gene expression in a hierarchical control structure. The scope of experimental methods in molecular biology for identifying the role of individual mechanisms in the overall hierarchy is limited to a subset of the total in vivo interactions. Quantitative analyses have been used .