A Combined Pathway to Simulate CDK-Dependent Phosphorylation and ARF-Dependent Stabilization for p53 Transcriptional Activity

Atsushi Doi[1] (doi@ims.u-tokyo.ac.jp)
Masao Nagasaki[1] (masao@ims.u-tokyo.ac.jp)
Kazuko Ueno[1] (uepi@ims.u-tokyo.ac.jp)
Hiroshi Matsuno[2] (matsuno@sci.yamaguchi-u.ac.jp)
Satoru Miyano[1] (miyano@ims.u-tokyo.ac.jp)

[1]Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
[2]Graduate School of Science and Engineering, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, 753-8512, Japan


The protein p53 is phosphorylated by a member of protein kinases such as CDK7, and stabilized by the protein ARF. The phosphorylation and stabilization of p53 is believed to enhance its transcriptional activity and act simultaneously. Biological pathways composed of experts knowledge obtained from the literature are including these activation mechanisms. However, the map of biological pathways does not reflect the combination effect of phosphorylation and stabilization. We have conducted some simulations of biological pathways with hybrid functional Petri net (HFPN) after careful reading of papers. In this paper, we constructed the HFPN based biological pathway of CDK-dependent phosphorylation pathway and combine with ARF-dependent pathway described previously, to observe the effect of the phosphorylation on the stabilization with simulation-based validation.

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Japanese Society for Bioinformatics