Fig. 1

Mechanisms of c-Myc protein stabilization and degradation. The phosphorylation of c-Myc at Serine 62 (S62) residue determines protein stabilization, c-Myc translocation into the nucleus and increased c-Myc transcriptional activity. S62 phosphorylation is essential for the subsequent phosphorylation at threonine 58 (T58) residue which in turns induces the removal of the phosphate group at S62. The singly phosphorylated T58-Myc is unstable being finally recognized by the Fbxw7 ubiquitin ligase and degraded by the 26S proteasome. S62 is phosphorylated by different types of kinases, including ERK, CDKs, and JNK, whereas T58 can be phosphorylated by GSK-3β kinase or by BRD4 protein [30]. T58 phosphorylation by GSK-3β and BRD4 can be inhibited by AKT and ERK, respectively