Protein kinase C enables the regulatory circuit that connects membrane synthesis to ribosome synthesis in Saccharomyces cerevisiae

The balanced growth of a cell requires the integration of major systems suc h as DNA replication, membrane biosynthesis, and ribosome formation. An exa mple of such integration is evident from our recent finding that, in Saccha romyces cerevisiae, any failure in the secretory pathway leads to severe re pression of transcription of both rRNA and ribosomal protein genes. We have attempted to determine the regulatory circuit(s) that connects the secreto ry pathway with the transcription of ribosomal genes. Experiments show that repression does not occur through the circuit that responds to misfolded p roteins in the endoplasmic reticulum, nor does it occur through circuits kn own to regulate ribosome synthesis, e.g. the stringent response, or the cAM P pathway. Rather, it appears to depend on a stress response at the plasma membrane that is transduced through protein kinase C (PKC), Deletion of PKC 1 relieves the repression of both ribosomal protein and rRNA genes that occ urs in response to a defect in the secretory pathway. We propose that failu re of the secretory pathway prevents the synthesis of new plasma membrane. As protein synthesis continues, stress develops in the plasma membrane. Thi s stress is monitored by Pkc1p, which initiates a signal transduction pathw ay that leads to repression of transcription of the rRNA and ribosomal prot ein genes. The importance of the transcription of the 137 ribosomal protein genes to the economy of the cell is apparent from the existence of at leas t three distinct pathways that can effect the repression of this set of gen es.