Mechanistic Insights into the Generation and Transduction of Hedgehog Signaling

Xiaofeng Qi, Xiaochun Li

Research output: Contribution to journalReview article

3 Scopus citations

Abstract

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 the Dispatched-1 (DISP1) and Scube2 proteins. The 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 discuss the recent structural and biochemical studies on four major components of the HH pathway: the 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 the treatment of HH-related diseases.

Original languageEnglish (US)
Pages (from-to)397-410
Number of pages14
JournalTrends in biochemical sciences
Volume45
Issue number5
DOIs
StatePublished - May 2020

Keywords

  • Dispatched
  • Hedgehog
  • Patched
  • signal transduction
  • Smoothened
  • sterol

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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