Molecular Interaction Maps--A Diagrammatic Graphical Language for Bioregulatory Networks

Abstract

Molecular interaction maps (MIMs) use a clear, accurate, and versatile graphical language to depict complex biological processes. Here, we discuss the main features of the MIM language and its potential uses. MIMs can be used as database resources and simulation guides, and can serve to generate new hypotheses regarding the roles of specific molecules in the bioregulatory networks that control progression through the cell cycle, differentiation, and cell death.

Tetrandrine Induces Early G1 Arrest in Human Colon Carcinoma Cells by Down-Regulating the Activity and Inducing the Degradation of G1-S–Specific Cyclin-Dependent Kinases and by Inducing p53 and p21Cip1

“…Cell cycle is regulated by a series of checkpoints monitoring genomic integrity and ensuring that DNA replication proceeds in a coordinated manner (5,14). Different combinations of CDK and cyclin subunits operate at checkpoint controls during the cell cycle to integrate mitogenic and antiproliferative signals.…”

“…Aberrations in cell cycle progression occur in the majority of human malignancies (see refs. 2,3,5,17). Whereas cell proliferation and differentiation are specifically controlled in the G 1 phase and the G 1 -S transition in the cell cycle, oncogenic progresses exert their greatest effect by targeting particular regulators of G 1 phase progression (31).…”

“…An additional positive feedback is exerted at the level of E2F1, which stimulates its own transcription. Thus, positive feedback on E2F1 and cyclin E produces a rapid increase of both activities as cells approach the G 1 -S boundary (5). In concert with the irreversible commitment to enter S phase, inactivation of Rb shifts from being mitogen dependent (cyclin D driven) to mitogen independent (cyclin E driven).…”

“…Throughout this interval, cyclin E is bound to and activates its catalytic partner CDK2. Because the cyclin E gene is itself E2F responsive, a positive feedback cyclin E-CDK2 loop acts to facilitate progressive rounds of Rb phosphorylation and E2F release (4,5,13). An additional positive feedback is exerted at the level of E2F1, which stimulates its own transcription.…”

“…At the molecular level, the restriction point is mediated by the retinoblastoma protein (Rb)-E2F pathway under the control of two families of regulatory enzymes, the cyclin D-and cyclin E-dependent kinases (CDKs; refs. [2][3][4][5].…”