Supplementary information for “ Stress - specific response of the p 53 - Mdm 2 feedback loop ”

Parameter values There are 9 parameters in these equations. Some can be fixed or constrained using data from literature: 1. p53 does not measurably degrade over 120 min in the absence of Mdm2 [1]. Therefore, its Mdm2independent degradation rate, α, is very low. We took α = 0.1hr, corresponding to a half life of 7.5 hours. In any case, as shown in Fig. 3 of the main text, varying α by upto 5-fold up or down makes no difference to the behaviour of the model. 2. The Mdm2 mRNA half-life has been measured to be 1–2 hours [2,3], so we fixed β = 0.6hr corresponding to a half-life of a little over 1 hr. 3. kb has been measured in ref. [4] to be 1.4 to 2 s . We therefore fix kb = 7200hr . 4. The dissociation constant kD ≡ kb/kf of the p53-Mdm2 complex has been reported to be various numbers, ranging from 100 molecules [5] (around 0.2 nM), to 60 nM [4] to 700 nM [4]. This implies kf should lie in the range 10–36,000 nMhr. 5. The Mdm2-dependent half-life of p53 was measured to be less than 15 min [1]. We therefore explored δ in the range 1–20 hr, corresponding to a half-life in the range 2–40 min.