The Dynamics Research Of P21 Accumulation Problems

Previous theoretical research about the start of the P53 and Mdm2 network,other genes and proteins affecting P53-Mdm2 osciallator behavior and the dynamic or biology research behaviors of the network have been well understood. But the theoretical study how to accomplish its"P53 tumor suppressor genes function"and how to initiate a range of its downstren genes to play a role is more superficial. This Review focuses on the regulation of P21(the most important downstream of P53) and its biological functions with emphasis on its promoting cell cycle arrest in response to many stimuli.So it is the P21 that helps P53 become tumour suppressor.This review will briefly discuss contents below: (1) the accumulation of P21 ;(2) P21-induced cell cycle arrest after DNA damage.There is growing evidence that post-transcriptional and post translational regulations play a critical role in P21 expression and activity.Even because of different signal characters ,P21 accumulate in different ways.This paper focuses on analyseing the cells after stimulated by ionizing radiation(IR),the accumulation mechanism of P21.Three mathematical models have been developed.Recent studies suggest that :at the beginning of IR,ATM directly medicates the phosphorylation of P21, in this process"Wortmannin"as an inhibitor. When P53 network is activated,P53 can trigger and activated P21 in two ways,including promoting the transcription and phosphorylation of P21. We construct some P21 dynamical models: (1) in normal cells ,(2) in the absence of quantitative ATM ,(3) with the"Wortmannin"the effect of ATM on P21,(4) the effect of different ATM on P21.According to the phosphorylation and dephosphorylation, we developed the second models:ATM-induced P21 accumalation .This model accord with Agami's study.Next we proposed another model of P21 accumulation which is dependent on P53.When the level of P21 reaches a certain threshold,it can launch a series of its downstream genes or protein to play a role of biology,making the cell cycle arrest and then leave enough time to omplete DNA repair.Finally we futher studies the protein network involving the cell cycle arrest and develop the mathematical model whith P21 as the lead-up ,Cyclin-CDK as the core of the network, simulating the condition and process of G1/S cell cycle arrest,which is consistent with previous experiment.