Transcriptional and Post-Transcriptional Regulation of Thrombospondin-1 Expression: A Computational Model
Fig 5
Dynamics of SMADs and TSP-1 protein synthesis.
(A) SMAD7, whose expression is induced by TGFβ activation, binds the RSMAD-receptor complex and prevents the phosphorylation of the RSMAD in the complex. (B) SMAD4 abundance is negatively regulated by SMAD7 since accumulated SMAD7 promotes SMAD4 degradation. (C) RSMAD-receptor complex sequestered by SMAD7 upon TGFβ activation is released when SMAD7 expression decreases, giving rise to the tail expression of activated RSMAD-SMAD4. (D) Inhibition of SMAD7 protein synthesis removes the tail expression but significantly prolongs the RSMAD-SMAD4 activation signals. (E) TSP-1 protein synthesis stimulated by different doses of TGFβ and (F) the corresponding dose response curve produced by the model. The peaks of total intracellular TSP-1 levels are normalized with respect to the maximum peak observed in the simulation of 20 ng/ml TGFβ stimulation. X-axis is in log scale.