GLI1 (glioma-associated oncogene homologue 1) is a central effector of the Hedgehog (HH) pathway, a pathway that governs many developmental processes []. It is a member of the GLI family of transcription factors, which also includes GLI2 and GLI3 []. GLI1 is an obligatory activator, whereas GLI2 and GLI3 carry activator and repressor functions []. GLI1 is amplified in a subset of human tumours []. It contains five repeats of a zinc finger DNA-binding motif and binds DNA in a sequence-specific fashion [, ].
GLI3 is a member of the GLI family of transcription factors, which also includes GLI1 and GLI2. They are central effectors of the Hedgehog (Hh) pathway in vertebrates [, ]. GLI1 is an obligatory activator, whereas GLI2 and GLI3 carry activator and repressor functions []. The full-length GLI3 form, after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while its C-terminally truncated form acts as a repressor (GLI3R). GLI3 participates in the patterning and growth of many organs, including the central nervous system (CNS) and limbs [, , , , ].
Rab23 is a member of the Rab family of small GTPases. In mouse, Rab23 has been shown to function as a negative regulator in the sonic hedgehog (Shh) signaling pathway. Rab23 mediates the activity of Gli2 and Gli3, transcription factors that regulate Shh signaling in the spinal cord, primarily by preventing Gli2 activation in the absence of Shh ligand []. Rab23 also regulates a step in the cytoplasmic signal transduction pathway that mediates the effect of Smoothened (one of two integral membrane proteins that are essential components of the Shh signaling pathway in vertebrates) [, ].In humans, Rab23 is expressed in the retina []. Mice contain an isoform that shares 93% sequence identity with the human Rab23 and an alternative splicing isoform that is specific to the brain. This isoform causes the murine open brain phenotype, indicating it may have a role in the development of the central nervous system [, ]. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins [].
This entry includes a group of zinc finger transcription regulators, including GLI1-3 and GLIS1/3 from humans.GLI1-3 are central effectors of the Hedgehog (Hh) pathway in vertebrates [, ]. GLI1 is an obligatory activator, whereas GLI2 and GLI3 carry activator and repressor functions []. The full-length GLI3 form, after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while its C-terminally truncated form acts as a repressor (GLI3R). GLI3 participates in the patterning and growth of many organs, including the central nervous system (CNS) and limbs [, , , , ].GLIS1/3 play key roles in the regulation of a number of physiological processes and have been implicated in several pathologies. Glis1-3 share a highly homologous zinc finger domain (ZFD) containing five Cys2-His2-type zinc finger (ZF) motifs with members of the Gli and Zic family [].
