Regulation of hedgehog signal transduction by ubiquitination and deubiquitination

Qing Zhang, Jin Jiang

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations


The Hedgehog (Hh) family of secreted proteins governs embryonic development and adult tissue homeostasis in species ranging from insects to mammals. Deregulation of Hh pathway activity has been implicated in a wide range of human disorders, including congenital diseases and cancer. Hh exerts its biological influence through a conserved signaling pathway. Binding of Hh to its receptor Patched (Ptc), a twelve-span transmembrane protein, leads to activation of an atypical GPCR family protein and Hh signal transducer Smoothened (Smo), which then signals downstream to activate the latent Cubitus interruptus (Ci)/Gli family of transcription factors. Hh signal transduction is regulated by ubiquitination and deubiquitination at multiple steps along the pathway including regulation of Ptc, Smo and Ci/Gli proteins. Here we review the effect of ubiquitination and deubiquitination on the function of individual Hh pathway components, the E3 ubiquitin ligases and deubiquitinases involved, how ubiquitination and deubiquitination are regulated, and whether the underlying mechanisms are conserved from Drosophila to mammals.

Original languageEnglish (US)
Article number13338
JournalInternational journal of molecular sciences
Issue number24
StatePublished - Dec 1 2021


  • Ci
  • DUB
  • Deubiquitination
  • E3
  • Gli
  • Ptc
  • Ptch1
  • Smo
  • Ubiquitination
  • hedgehog

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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