Roles of Protein Ubiquitination and Degradation Kinetics in Biological Oscillations
نویسندگان
چکیده
Protein ubiquitination and degradation play important roles in many biological functions and are associated with many human diseases. It is well known that for biochemical oscillations to occur, proper degradation rates of the participating proteins are needed. In most mathematical models of biochemical reactions, linear degradation kinetics has been used. However, the degradation kinetics in real systems may be nonlinear, and how nonlinear degradation kinetics affects biological oscillations are not well understood. In this study, we first develop a biochemical reaction model of protein ubiquitination and degradation and calculate the degradation rate against the concentration of the free substrate. We show that the protein degradation kinetics mainly follows the Michaelis-Menten formulation with a time delay caused by ubiquitination and deubiquitination. We then study analytically how the Michaelis-Menten degradation kinetics affects the instabilities that lead to oscillations using three generic oscillation models: 1) a positive feedback mediated oscillator; 2) a positive-plus-negative feedback mediated oscillator; and 3) a negative feedback mediated oscillator. In all three cases, nonlinear degradation kinetics promotes oscillations, especially for the negative feedback mediated oscillator, resulting in much larger oscillation amplitudes and slower frequencies than those observed with linear kinetics. However, the time delay due to protein ubiquitination and deubiquitination generally suppresses oscillations, reducing the amplitude and increasing the frequency of the oscillations. These theoretical analyses provide mechanistic insights into the effects of specific proteins in the ubiquitination-proteasome system on biological oscillations.
منابع مشابه
Chemical Composition, Ruminal Dry Matter, Crude Protein andCell Wall Degradation Kinetics of Pasture Forages Dominant in the West Provinces of Iran
The objectives of this study were to determine and compare the chemical composition and ruminal degradability of dry matter (DM), crude protein (CP), neutral detergent fiber (NDF) and acid detergent fiber (ADF) of ten pasture forage species dominant in the west provinces of Iran. Duplicate nylon bags of pasture samples were suspended in the rumen of four wethers for up to 96 h. The chemical com...
متن کاملDegradation of antizyme inhibitor, an ornithine decarboxylase homologous protein, is ubiquitin-dependent and is inhibited by antizyme.
Ornithine decarboxylase (ODC) is the most notable example of a protein degraded by the 26 S proteasome without ubiquitination. Instead, ODC is targeted to degradation by direct binding to a polyamine-induced protein termed antizyme (Az). Antizyme inhibitor (AzI) is an ODC-related protein that does not retain enzymatic activity yet binds Az with higher affinity than ODC. We show here that like O...
متن کاملComparison of in vitro Fermentation with in situ Degradation to Estimate Dry Matter Degradability and Energy Protein Synchronization of Roughage Based Diets
This study was aimed to evaluate the correlation between in vitro fermentation and in situ degradation parameters and to predict dry matter degradability and energy protein synchronization of roughage based diets. Different inclusion of roughage in diets [roughage 50% diet (R50D), roughage 60% diet (R60D), roughage 65% diet (R65D) and roughage ...
متن کاملRuminal Degradation Kinetics of Wheat Straw Irradiated by High Doses of Electron Beam
This study was conducted to evaluate the effect of electron beam irradiation at doses of 250 and 500 kGy on the chemical composition and ruminal dry matter (DM) and neutral detergent fiber (NDF) degradability of wheat straw. Nylon bags of untreated or irradiated wheat straw were suspended in the rumen of three rams for up to 72 h, and resulting data were fitted to non-linear degradation model t...
متن کاملSwitches, Excitable Responses and Oscillations in the Ring1B/Bmi1 Ubiquitination System
In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating...
متن کامل