Figure 8.

Potential biological roles of the I2PP2A-ceramide interaction in the regulation of c-Myc degradation via control of PP2A. Results provided in this study indicate that I2PP2A-ceramide binding reveals a novel mechanism for ceramide-mediated activation (relief of repression) of PP2A activity when I2PP2A expression is decreased (left panel), leading to c-Myc dephosphorylation and degradation. It is still not known whether ceramide-mediated activation of GSK3-β is also involved in this process. On the other hand, overexpressed I2PP2A traps ceramide, which leads to repression of PP2A, resulting in decreased dephosphorylation of c-Myc at S62 (right panel), increased stability of c-Myc, and protection of cells from the antiproliferative roles of ceramide.