FIGURE 12.

Proposed model for differential fates of R-CRT and mechanism for cyt-CRT and R-CRT degradation. The arrow thickness is proportional to efficiency of the process. CRT is synthesized in the ER, where its signal peptide is cleaved by peptide hydrolases to release the mature protein. CRT retrotranslocated to the cytoplasm is arginylated by Ate1 to generate R-CRT. Both isoforms can be degraded by proteasomes, but only R-CRT is ubiquitinated, suggesting that different proteasomal degradation mechanisms are involved. The CRT and R-CRT populations can be partially dimerized in different proportions. Under stress conditions, only R-CRT is recruited to SGs. When the stress exceeds a threshold value, R-CRT also appears in the plasma membrane. The indicated R-CRT locations are responsible for interfering with proteasomal degradation and increasing metabolic stability.