NguyenLK2011 - Ubiquitination dynamics in Ring1B/Bmi1 system

NguyenLK2011 - Ubiquitination dynamics in
Ring1B-Bmi1 system
This theoretical model investigates the
dynamics of Ring1B/Bmi1 ubiquitination to identify bistable
switch-like and oscillatory behaviour in the
system. Michaelis-Menten (MM) equations are used to formulate
the model. However, the authors show that the dynamics persist even
for Mass-Action kinetics. This SBML file is the MM version of the
model.

This model is described in the article:

Switches,
excitable responses and oscillations in the Ring1B/Bmi1
ubiquitination system.

Nguyen LK, Muñoz-García J,
Maccario H, Ciechanover A, Kolch W, Kholodenko BN.
PLoS Comput. Biol. 2011 Dec; 7(12):
e1002317
Abstract:

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 oscillations
between its distinct ubiquitination and activity states. These
different Ring1B states display canonical or multiply branched,
atypical polyubiquitin chains and involve association with the
Polycomb-group protein Bmi1. Bistable switches and oscillations
may lead to all-or-none histone H2A monoubiquitination rates
and result in discrete periods of gene (in)activity. Switches,
overshoots and oscillations in Ring1B catalytic activity and
proteosomal degradation are controlled by the abundances of
Bmi1 and Ring1B, and the activities and abundances of external
ligases and deubiquitinases, such as E6-AP and USP7.

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