Ongoing DNA synthesis in the rat cerebral cortex is regulated by a proteolytic pathway independent of the proteasome and calpains

摘要

By using mini-units of tissue and protease inhibitors in short term incubation (0–180 min), we studied the role of proteolysis for ongoing DNA replication in the developing rat cerebral cortex. The protease inhibitors TLCK, TPCK, PMSF, MG-132 and PSI markedly inhibited DNA synthesis. The inhibitory effects were concentration-dependent and of early onset (within 60 min). The most selective proteasome inhibitors lactacystin and clasto-lactacystin-β-lactone as well as the calpain inhibitor I and II had no or minimal effects on DNA synthesis. Only high concentrations of calpain inhibitor I (≥ 250 μM) and calpain inhibitor II (≥ 500 μM) gave a DNA synthesis inhibition. These results suggest that (1) ongoing DNA replication is regulated by proteolysis and (2) the proteolytic pathways involved are neither the proteasome nor the calpains.