0& 0& 0\\
0 & 0 & 0 & 1& -1 & 0\\
0 & 0 & 0 & 0 & 1 & -1\end{array} \right],\end{aligned}$$ where $x$ is the concentration of p53, $y_0$ the concentration of precursor of Mdm2, $y$ is the concentration of Mdm2, $k_1$ is the p53 production rate, $k_2$ is the Mdm2-independent p53 degradation rate, $k_{3}$ the saturating p53 degradation rate, $k_{7}$ is the p53 threshold for degradation by Mdm2, $k_{4}$ is the p53-dependent Mdm2 production rate, $k_5$ is the Mdm2 maturation rate and $k_6$ is the Mdm2 degradation rate.

Figure \[p53figure1\]a shows an SSA simulation of the model for parameters $q_1=$\[90,0.002,1.7,1.1,0.93,0.96,0.01\] and initial values $\textbf{x}(0)=[70, 30, 60]$, which exhibits oscillating behaviour. Because the oscillations for different realisations of the SSA (corresponding to different cells) are stochastically out of phase, the average over 100,000 stochastic simulations shows a damped oscillation, reflecting the presence of a negative feedback loop. Figures \[p53figure1\]c-h show the trajectories of the mean calculated with the moment approximation method. In the deterministic approximation, the oscillations are not damped but expanding, which would indicate a positive instead of negative feedback loop. The LNA and the 2 moment approximation show the same effect. The mean calculated 