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Fig. 5. Interactions of p53, MDM2, and ARF described in TRANSPATH. This map includes ubiquitination of protein p53 by
protein MDM2 and degradation of protein p53 by proteasome. In addition, the following facts are described: acetylated and
phosphorylated p53 proteins have transcriptional activity by forming tetramer, and ARF-INK4a forming complex with MDM2
localizes in the nucleolus.
ARF, ubiquitination of p53 by the complex of MDM2 and ARF is not involved in this map while the
effect of tetramer formation of protein p53 is involved.
3
Figure 6 shows the relationships among proteins p53, MDM2, and p19ARF in the description proposed
by Kohn [Kohn, 1999], (
http://discover.nci.nih.gov/mim/index.jsp
). The arc terminated with the short
bar in this map represents repression of p53 degradation by the complex MDM2-p19ARF. The same
function as this repression of p53 degradation is involved in the HFPN model of Fig. 2, while this
function of repression is not modeled using such symbol of arc for repression. That is, the HFPN model
of Fig. 2 realizes this repression by transition
T
4
in Fig. 2, to which two arcs from places p53(N) and
MDM2 p19ARF connect, and from which an arc to place p53 MDM2 p19ARF connects. It is easily
seen that this complex formation of p53-MDM2-p19ARF prevents the protein p53 from degrading if
we notice the fact that p53 is degraded through the complex formation with protein MDM2. Hence,
the HFPN of Fig. 2 involves more exact description than Fig. 6 about the interactions of proteins p53,
MDM2, and p19ARF.
Note that the information interpreted into the HFPN model in Fig. 2 has been extracted by human
experts from the literature and it involves various biological facts as mentioned in section of HFPN
model. However, such information is not fully included in these molecular interaction maps.
DISCUSSION AND CONCLUSION
Through simulation, we discussed whether the complex p53-MDM2-p19ARF has transcriptional
activity for genes
Bax
and
MDM2
or not.
3
It is not clear from [Pomerantz
et al.
, 1998] whether protein p53 forms tetramer or remains as monomer.
