HKR1, GLI Kruppel Zinc Finger Family Member (HKR1)

HKR1 belongs to the krueppel C2H2-type zinc-finger protein family.GLI2-delta-N exhibited potent transcriptional activity in vivo: overexpression in mouse skin led to the formation of hedgehog-independent epithelial downgrowths resembling basal cell carcinomas, which in humans are associated with constitutive hedgehog signaling. On the basis of the functional domains affected by known human GLI2 mutations, mutant GLI2 proteins exhibited either loss-of-function or dominant-negative activity. Moreover, deletion of the N terminus abrogated dominant-negative activity of mutant GLI2, revealing that this domain may be required for transcriptional repressor activity of pathogenic GLI2. the N-terminal transcriptional repressor domain may play a critical role in modulating the function of wildtype GLI2 and may be essential for dominant-negative activity of a GLI2 mutant associated with human disease.