Gli1

The Hedgehog (Hh) family of secreted proteins is involved in a number of developmental processes, one of which is the development of cancer. Past data suggests that the Sonic hedgehog (Shh) receptor is composed of two transmembrane proteins, Patched and Smoothened.  The Hedgehog (Hh) signaling pathway is vital to the development of many tissues during embryogenesis, however, it also has an important role after development.  After development, Hh signaling regulates stem cells and their regenerative function.  When the Hh pathway is awry, signaling may turn oncogenic in nature.

SHARP1 encodes a transcription repressor factor that belongs to the Hairy/Enhancer of the Split subfamily of basic helix-loop-helix factors (bHLH). Sequence alignment shows that SHARP1 is only distantly related to these proteins with a 37-42% sequence identity within its bHLH domain. Unlike most other bHLH proteins, SHARP-1 is not expressed in neuronal progenitor cells or early differentiating neurons but is instead restricted to neuronal subset within the postnatal central nervous system (CNS).

Glioma-associated oncogene 1 (Gli1) is a transcription factor within the DNA-binding zinc-finger protein family. The Sonic Hedgehog signaling pathway (SHH), which assists in embryonic development and maintaining stem cell populations in adults, activates the Gli1 protein. In the SHH Pathway, the hedgehog ligand binds to patched transmembrane protein receptor (PTC). PTC is an inhibitor of SMO, a protein receptor, and when the hedgehog ligand is present, SMO is not inhibited.

The Hedgehog Signaling Pathway (HSP) is an important pathway involved in embryonic development by regulating cell differentiation. This pathway has also become an increasingly hot topic in cancer research in recent years. The HSP involves the interaction between several targets to activate members of the Gli family of transcription factors, such as Gli1, Gli2, and Gli3.