Mechanisms of smoothened regulation in hedgehog signaling

Jie Zhang, Zulong Liu, Jianhang Jia

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


The seven-transmembrane protein, Smoothened (SMO), has shown to be critical for the hedgehog (HH) signal transduction on the cell membrane (and the cilium in vertebrates). SMO is subjected to multiple types of post-translational regulations, including phosphorylation, ubiquiti-nation, and sumoylation, which alter SMO intracellular trafficking and cell surface accumulation. Recently, SMO is also shown to be regulated by small molecules, such as oxysterol, cholesterol, and phospholipid. The activity of SMO must be very well balanced by these different mechanisms in vivo because the malfunction of SMO will not only cause developmental defects in early stages, but also induce cancers in late stages. Here, we discuss the activation and inactivation of SMO by different mechanisms to better understand how SMO is regulated by the graded HH signaling activity that eventually governs distinct development outcomes.

Original languageEnglish
Article number2138
Issue number8
StatePublished - Aug 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Cholesterol
  • Hedgehog signaling
  • Phospholipid
  • Phosphorylation
  • Smoothened
  • Ubiquitination

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)


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