Mechanistic insights into the generation and transduction of Hedgehog Signaling

By Xiaofeng Qi, Xiaochun Li. 2020

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Cell differentiation and proliferation require Hedgehog (HH) signaling, and aberrant HH signaling causes birth defects or cancers. In this signaling pathway, the N-terminally palmitoylated and C-terminally cholesterylated HH ligand is secreted into the extracellular space with help of Dispatched-1 (DISP1) and Scube2 proteins. Patched-1 (PTCH1) protein releases its inhibition of the oncoprotein Smoothened (SMO) after binding the HH ligand, triggering downstream signaling events. In this review, we will discuss the recent structural and biochemical studies on four major components in HH pathway: HH ligand, DISP1, PTCH1, and SMO. This research provides mechanistic insights into how HH signaling is generated and transduced from the cell surface into the intercellular space and will aid in facilitating treatment of HH related diseases.

Subfields: Genetics, Molecular Biology