Degradation of Newly Synthesized Ribosomal Proteins and Histones in Regenerating Rat Liver with and without Treatment with a Low Dose of Actinomycin D

The metabolism of newly synthesized ribosomal proteins in regenerating livers of rats pretreated with a low dose of actinomycin D which selectively inhibits rRNA synthesis, has been investigated. After 15 min of labeling most newly synthesized proteins were found in the cell sap of regenerating livers of rats pretreated for 1 h with actinomycin D and disappeared from this fraction during a subsequent chase in the presence of cycloheximide. However, no proteinase activity for ribosomal proteins was detected in cell sap. After treatment in vivo with E‐64, a thiol‐proteinase inhibitor which inhibits the ribosomal protein‐hydrolysing activities of nuclear and mitochondrial plus lysosomal fractions of rat liver, a fraction of newly synthesized ribosomal proteins was found to accumulate in nuclci of actinomycin‐ d ‐prctreated regenerating rat liver. These results may indicate that ribosomal proteins synthesized in the absence of rRNA synthesis accumulated in cell sap, and were then transported into nuclei where they were degraded by a proteinase sensitive to E‐64. In the absence of actinomycin D pretreatment smaller amounts of ribosomal proteins accumulated in nuclei of regenerating livers of E‐64‐treated rats. Furthermore, histones (except histone H1) also accumulated in nuclei of regenerating livers of E‐64‐treated rats with and without actinomycin D pretreatment. Thus, these two kinds of proteins, especially histones, are synthesized in excess of nascent rRNA or DNA, and are degraded preferentially in nuclei in regenerating rat liver.