Abstract
The molecular interactions implicated in the mammalian G1/S cell cycle phase transition comprise a highly non-linear network which can produce seemingly paradoxical results and make intuitive interpretations unreliable. A new approach to this problem is presented, consisting of (1) a convention of unambiguous reaction diagrams, (2) a convenient computer simulation method, and (3) a quasi-evolutionary method of probing the functional capabilities of simplified components of the network. Simulations were carried out for a sequence of hypothetical primordial systems, beginning with the simplest plausibly functional system. The complexity of the system was then increased in small steps, such that functionality was added at each step. The results suggested new functional concepts: (1) Rb-family proteins could store E2F in a manner analogous to the way a condenser stores electric charge, and, upon phosphorylation, release a large wave of active E2F; (2) excessive or premature cyclin-dependent kinase activities could paradoxically impair E2F activity during the G1/S transition period. The results show how network simulations, carried out by means of the methods described, can assist in the design and interpretation of experiments probing the control of the G1/S phase transition.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kohn, K. Functional capabilities of molecular network components controlling the mammalian G1/S cell cycle phase transition. Oncogene 16, 1065–1075 (1998). https://doi.org/10.1038/sj.onc.1201608
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201608
Keywords
This article is cited by
-
Quantitative and logic modelling of molecular and gene networks
Nature Reviews Genetics (2015)
-
A review of spatial computational models for multi-cellular systems, with regard to intestinal crypts and colorectal cancer development
Journal of Mathematical Biology (2013)
-
Towards a systems biology approach to mammalian cell cycle: modeling the entrance into S phase of quiescent fibroblasts after serum stimulation
BMC Bioinformatics (2009)
-
The Systems Biology Graphical Notation
Nature Biotechnology (2009)
-
A data integration approach for cell cycle analysis oriented to model simulation in systems biology
BMC Systems Biology (2007)