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“equilibrons” and “dissipatons.” Employing these new terms, we can describe the cell
in two distinct ways - (1)
phenomenologically
as a set of phenons, or (2)
mechanisti-
cally
as a set of spatiotemporally organized
equilibrons
and
dissipatons
. The phenom-
enological method of describing the living cell represents the traditional cell biology
that prevailed before the emergence of the Mendelian gene as a unit of inheritance and
before the mechanism-based way of describing the cell began to appear in the
early decades of the twentieth century, especially after the discovery of the double
helical structure of DNA by Watson and Crick in 1953. Interestingly, the concepts
of
equilibrons
and
dissipatons
that are postulated to be the building blocks of
all molecular mechanisms underlying life appear to be closely related to what
Darden (2006) refers to as “entities” and “activities” in her dualistic theory of
biological mechanisms.
The abstract concepts of
equilibrons
and
dissipatons
introduced in this topic can be
given some concreteness by illustrating their roles in the mechanism of action of p53.
The p53 protein was discovered in 1979 but its functionwas not established until 1989.
It suppresses tumors under normal conditions, and when mutated, loses its ability to
suppress tumors, leading to cancer (Vogelstein et al. 2000). About one-half of all
human tumors are known to be caused by (or associated with) mutated p53. In the so-
called p53 network described byVogelstein et al. (2000), the p53 protein plays the role
of a
hub
having at least 5 incoming links and 18 outgoing ones. Additionally, the
synthesis of p53 protein requires a set of other proteins to catalyze the translation step
and the presence of p53 mRNA as the template. The synthesis of p53 mRNA in turn
requires another set of about 50 proteins (in the form of a
transcriptosome
,aterm
coined by Halle and Meisterernst [1996]) to catalyze transcription and transcript
processing using the p53 gene as the template. Finally, the p53 protein acts as a
transcription factor for several dozens of genes by binding to specific sequences in
DNA, thereby activating the transcription of target genes (Vogelstein et al. 2000).
To represent all these complex mechanisms of interactions of p53 with other
ligands (DNA, RNA, proteins, and most likely some inorganic ions) and its biological
functions, it is almost mandatory to use the
language of networks
(Barabasi 2002).
Vogelstein et al. (2000) used a two-dimensional network for this purpose, but it
became obvious to me that the dimensionality of the network should be expanded to
at least eight. The eight dimensions include the traditional space and time coordinates
(x, y, z , and t) for localizing p53 molecule inside the cell at time t, three network-
related dimensions of
n
,
l,
and
f
(where
n
stands for
nodes
,
l
for
links
or
edges
,and
to characterize the higher-order organization (here called “stacking”) of the five
traditional networks to form what may be referred to as a “hypernetwork” or cell
“interactome,” the term “interactome” being defined here as the totality of molecular
interactions in living systems (cf.
Wikipedia.org/wiki/Interactome
). Thus, the eight-
dimensional hypernetwork (or
interactome
) of p53 can be graphically represented in
terms of the following elements and procedures (see Fig.
9.2
):
1. The two-dimensional network of genes (denoted by dots on the planes and the
edges omitted for simplicity) centered on the p53
gene
acting as a hub (see 1 on
Plane A or the Gene Space).
