PURIFICATION AND CHARACTERIZATION OF NUCLEOLIN AND ITS IDENTIFICATIONAS A TRANSCRIPTION REPRESSOR

Expression of the acute-phase response genes, such as that for alpha-1 acid glycoprotein (AGP), involves both positive and negative transcri ption factors. A. positive transcription factor, AGP/EBP, and a negati ve transcription factor, factor B, have been identified as the two mos t important factors responsible for the induction of the AGP gene. In this paper we report the purification, characterization and identifica tion of a B-motif-binding factor from the mouse hepatoma cell line 129 p. The purified factor has been identified as nucleolin by amino acid sequence analysis. Biochemical and functional studies further establis hed that nucleolin is a transcription repressor for regulation of AGP and possibly other acute-phase response genes. Thus, in addition to th e many known functions of nucleolin, such as rRNA transcription, proce ssing, ribosome biogenesis, and the shuttling of proteins between the cytoplasmic and nuclear compartments, it may also function as a transc riptional repressor.