Stability of Nucleolin protein as the basis for the differential expression of Nucleolin mRNA and protein during serum starvation.

Abstract

Nucleolin is a nucleolar phosphoprotein that plays a direct role in ribosome biogenesis. Our aim was to determine how its activity as a growth-promoting factor is coordinated with, if not regulated by, the cell cycle machinery. In serum starting and then rescuing these cells with serum, we found that the protein level did not drop in the same way that the mRNA level did. In addition, although the mRNA level rises during the immediate period during serum rescue, the protein level remained the same. We found that the protein level was maintained after serum starvation as a result of high stability. There was no selective enhanced translation of the remaining amount of Nucleolin mRNA. With regard to the constancy in protein level despite the rise in mRNA level during serum rescue, there is no concomitant degradation of newly synthesized or old protein and synthesis of new protein. Because Nucleolin has been documented to bind mRNA, APP mRNA being one among them, we propose a autoregulatory model in which Nucleolin regulates the translation of Nucleolin mRNA, such that during a period of excess protein, translation is inhibited through direct binding of Nucleolin protein to its mRNA.