Zinc finger protein GLI2 (GLI2) (GLI2)

Zinc finger protein GLI2 (GLI2) is a member of the Kruppel-like family of transcription factors and serves as a primary mediator of the Hedgehog (Hh) signaling pathway. It functions predominantly as a transcriptional activator, regulating genes essential for cell cycle progression, proliferation, and embryonic pattern specification. In the absence of Hh ligands, GLI2 is sequestered in the cytoplasm by Suppressor of Fused (SUFU) and undergoes proteolytic processing into a repressor form; upon pathway activation, it translocates to the nucleus to initiate gene expression. Aberrant GLI2 activity is a hallmark of several malignancies, including basal cell carcinoma and medulloblastoma, and is also implicated in kidney fibrosis. Because GLI2 operates downstream of Smoothened (SMO), it represents a vital therapeutic target for overcoming resistance to clinical SMO inhibitors like vismodegib. Current drug development efforts focus on small molecules such as GANT61 and arsenic trioxide that directly inhibit GLI2-DNA binding or promote its degradation.

Other names

Glioma-associated oncogene 2GLI family zinc finger 2HPE6THP1THP2CJSHPE9PHS2

Inhibition of GLI-mediated transcription through direct binding to the zinc finger domain to prevent DNA interaction, induction of protein degradation, or prevention of nuclear translocation.