Translational control at the level of initiation of protein synthesis The effect of 3-methylcholanthrene administration on the activity of rat liver IF-M 2 A, IF-M 2 B and IF-M 3

Abstract

1. 1. In order to determine how pharmacological agents might alter the intracellular rates of protein synthesis at the translational level, the protein synthesis initiation factors present in a crude 0.5 M KCl microsomal wash fraction were isolated from livers of immature rats that had been injected either 2 or 17 h earlier with the polycyclic hydrocarbon 3-methylcholanthrene. These initiation factors were then tested for their ability to stimulate natural mRNA-directed protein synthesis in a highly fractionated cell-free protein-synthesizing system derived from rabbit reticulocytes. 2. 2. Greater initiation factor activity was observed when IF-M 2 A and IF-M 2 B were isolated from the livers of 3-methylcholanthrene-pretreated rats. Liver IF-M 3 preparations from both control and 3-methylcholanthrene-pretreated rats were equally efficacious in stimulating protein synthesis. The greater stimulatory effect of IF-M 2 A or IF-M 2 B isolated from 3-methylcholanthrene-pretreated rat liver was blocked by specific inhibitors of initiation, aurintricarboxylic acid and NaF. More importantly, incorporation in both controls and experimentals was reduced to the blank level as would be seen in the absence of initiation factors, further indicating that the effect of 3-methylcholanthrene is at the level of initiation. 3. 3. The role of the protein synthesis initiation factors in the altered rates of protein synthesis which accompany cytodifferentiation and growth in this, as well as other systems, is discussed.