FIGURE 6.

A new pathway in diseases; zinc deficiency leads to overproduction of Hh ligand and the activation of Hh signaling pathway. Under normal physiological conditions, zinc binds to Hint domain on Hh precursor and inhibits Hh autoprocessing and Hh signaling pathway. When the zinc level is low, Hh autoprocessing will be enhanced, leading to overproduction of Hh ligand. Hh ligand binds to Patched (PTCH), relieving its inhibition of Smoothened (SMO). Smoothened in turn activates Gli transcription factors, turning on the transcriptions of Hh target genes. The low zinc-high Hh axis may contribute to the pathogenic mechanisms of many types of cancer and ASD.