MicroRNAs and Robustness in Biological Regulatory Networks. A Generic Approach with Applications at Different Levels: Physiologic, Metabolic, and Genetic - Systems Biology of Metabolic and Signaling Networks - page 89

Fig. 4.16 Engrailed control network with its regulatory environment of up- or down-subnetworks.
The number and nature of attractors of subnetworks are indicated in blue . Green or white -headed
arrows correspond to inhibitions, red or black -headed to activations

MAPK, Engrailed, GATA-6, c-MyC, p53, miRNA34, Cdk2, E2F, RAS, and
caspases, through the microRNAs miR34 and miR302, to enter in the limit cycle:

ð ; ; ; Þ:

000000110110 011000010010 111101000011 100111100011

Then, the E2F/proliferation box is activated 1 time out of 4 and the apoptosis box
1 time out of 2, such as we observe the following cyclic behavior: 4 cells, 4 cells,
3 cells, 2 cells, 4 cells, etc. This dynamic behavior allows the exponential growth of
proliferation compensating exactly in a tissue the linear growth of apoptosis—two
daughter cells replacing two dead cells during one period of the limit cycle, hence
ensuring the conservation of the tissue volume and function. If the double dual
control (acceleration and brake) by c-Myc is no more ensured, a pathologic
proliferation (like in cancerogenesis) or excessive cell death (like in aging) can
occur (Table 4.8 ).