Figure 6.

Model of SCP1 phosphoregulation of REST function. A, when REST is phosphorylated at Ser-861 and/or Ser-864, the SCF^β-TRCP complex targets the Ser-1024/27/30 degron and ubiquitinates REST for degradation. Dephosphorylation at the Ser-861 and Ser-864 sites of REST by SCP1 prevents the SCF^β-TRCP complex from stably associating with the Ser-1024/27/30 degron. Unphosphorylated REST recruits various regulatory factors to RE1 elements and represses neuronal gene expression. B, inactivation of SCP1 by small molecule inhibitors should conversely lead to increased Ser-861 and Ser-864 phosphorylation followed by increased REST degradation and finally induction of RE1-associated neuronal genes.