A Hill type equation reveals the regulation principle of target protein expression led by p53 pulsing

Abstract

AbstractThe central dogma indicates the basic direction of gene expression pathways. For activated gene expression, the relationship between various links from the binding of transcription factor (TF) DNA to protein synthesis remains unclear. There is consensus that at a steady state, protein levels are largely determined by the mRNA level. How can we determine this steady state? Taking p53 as an example, based on the previously discovered Hill-type equation that characterizes mRNA expression under p53 pulsing, I proved that the same equation can be used to describe the average steady state of target protein expression. Therefore, at the steady state, the average fold changes of mRNA and protein expression under TF pulsing are the same. This consensus has been successfully demonstrated. For the geneBAXof the p53 target, the observed fold changes in mRNA and protein were 1.72, 1.28, respectively; the mRNA and protein expressions calculated using the Hill-type equation were 1.35. Therefore, using this equation, we are not only able to fine-tune gene expression, but also to predict the proteome from the transcriptome. Furthermore, by introducing two quantitative indicators, we can understand the degree of accumulation and stability of protein expression.