Fig. 4
From: GLI3: a mediator of genetic diseases, development and cancer
Regulation of GLI3-FL and GLI3-R. GLI3-FL (but not GLI3-R) is proteasomally degraded upon overexpression of SPOP, while binding by CBP, Androgen receptor, MED12, SET7 and release of PP2A stabilizes GLI3-FL and facilitates its translocation to the nucleus. GLI3-R generation is facilitated by SUFU recruitment of Gpr161, which activates PKA. PKA phosphorylates GLI3 at AA residues 849, 865, 877, 907, 980 and 1006. This phosphorylation leads to hyperphosphorylation by GSK3β (AA 841-880) and binding of βTrCP to GLI3. βTrCP then recruits SCFTrCP which ubiquitinates GLI3 leading to proteasomal cleavage and generation of GLI3-R which can translocate to the nucleus to regulate gene expression (Figure created with BioRender.com)