Biology Reference
In-Depth Information
Table 2
Places in the HFPN model of Fig. 2
Place Name
Variable (
mX
)
Initial Value
p53(N)
m
1
0
MDM2(N)
m
2
0
p53 MDM2 p19ARF
m
3
0
p19ARF(N)
m
4
0
p53 MDM2(N)
m
5
0
MDM2 p19ARF
m
6
0
p53 MDM2(C)
m
7
0
Ubiquitin
m
8
100
p53[Ub]
m
9
0
p53 mRNA
m
10
0
p53(C)
m
11
0
MDM2(C)
m
12
0
MDM2 mRNA
m
13
0
m
14
Bax mRNA
0
m
15
p19ARF mRNA
0
m
16 0
Variable (
mX
(
X
=
1,
...
, 16)) indicates a concentration
of each substance. Initial Value is a initial content of a
place.
p19ARF(C)
processes are described in the fourth column of Table 1 with the literature in the fifth column. Table 2
summarizes variable and initial value of the place in the Fig. 2. Note that the transitions
d
j
(
j
=
1,
...
, 15) represent natural degradation of the corresponding substances. We define the speed of natural
degradation as
mX
*0.01(
mX
indicates the concentration of a corresponding substance).
By means of these transitions and notations for molecules, the molecular interactions in the pathway
can be described as follows: Protein p53 in the nucleus (p53(N)) forms complex with MDM2(N) (
T
1
),
migrating to the outside of the nucleus (
T
7
) (p53 MDM2(C)). Then with ubiquitin, p53 MDM2(C)
produces p53[Ub] (
T
8
) which will be decomposed by proteasome (
T
9
). Hence, the complex formation
of p53 MDM2(N) decreases the concentration of protein p53 in the nucleus (p53(N)). In contrast,
p19ARF(N) forms trimer p53 MDM2 p19ARF with proteins p53(N) and MDM2(N), thereby preventing
p53(N) from decreasing. There are two pathways to form the trimer p53 MDM2 p19ARF: One is the
case that p19ARF(N) is bound to complex p53 MDM2(N) (
T
3
) after forming the complex of p53(N) and
MDM2(N) (
T
1
), and the other is the case that p53(N) is bound to complex MDM2 p19ARF (
T
4
) after
forming the complex of MDM2(N) and p19ARF(N) (
T
2
). Consequently, p19ARF(N) prevents p53(N)
from decreasing because p53 MDM2 p19ARF can not be transferred to the cytoplasm, not being marked
with ubiquitin. After degradation of protein p53 of the heterodimer p53 MDM2(C) by proteasome (
T
8
and
T
9
), the remaining MDM2(C) migrates (
T
10
) to the inside of the nucleus (MDM2(N)).
Gene
p53
is transcribed (
T
5
) and translated (
T
6
) to produce protein p53(C), then it is migrated (
T
11
)
to the inside of the nucleus (p53(N)). The fact that p53(N) can contribute to the transcription of gene
MDM2
is expressed in this HFPN model by describing a test arc from place p53(N) to transition
T
18
.
Transitions
T
12
and
T
14
are used for expressions of
MDM2
and
p19ARF
, respectively. Translations
of genes
MDM2
and
p19ARF
are represented by transitions
T
13
and
T
15
, respectively. Transition
T
16
represents the nuclear import of protein p19ARF.
Activation of gene
Bax
by protein p53(N) is represented by a test arc from place p53(N) to transition
T
17
. Experimentally, the transcriptional activity of protein p53 is detected by the concentration of
Bax
mRNA, and this is a reason why gene
Bax
appears in Fig. 2.
