The ubiquitin-proteasome system in melanin metabolism

J Cosmet Dermatol. 2022 Dec;21(12):6661-6668. doi: 10.1111/jocd.15433. Epub 2022 Oct 25.


Background: The ubiquitin-proteasome system (UPS) is a highly conserved way of regulating intracellular protein balance. UPS mediates proteolysis and disruption of variation or misfolding, while finely regulating proteins involved in differentiation and other biological processes.

Aims: The aim of this review is to systematically introduce UPS as a key regulator of melanin metabolism.

Methods: Systematic search and retrospective review were performed on the published data.

Results: Melanocyte-inducing transcription factor (MITF) is a substrate of the ubiquitin ligase VCHL1 and acts as a transcription factor to regulate the expression of key enzymes in melanin synthesis such as tyrosinase (TYR). The rate-limiting enzyme TYR is modified by the ubiquitin ligase Hrd1 during melanosynthesis. Melanin itself is also regulated by multiple ubiquitin ligases including Fbp1 and Vhl. By regulating the ubiquitination modification to target each link of melanin synthesis, it plays an important role in correcting the disorder of melanin metabolism. A number of chemical agents have been proven to inhibit the activity of ubiquitin ligase.

Conclusions: Drugs targeting E3 ligase and deubiquitinating enzymes have great potential in the treatment of melanin metabolism disorders.

Keywords: melanin; melanocyte-inducing transcription factor; tyrosinase; ubiquitin-proteasome system.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Humans
  • Melanins
  • Proteasome Endopeptidase Complex* / metabolism
  • Transcription Factors
  • Ubiquitin* / metabolism
  • Ubiquitin-Protein Ligases / metabolism


  • Melanins
  • Proteasome Endopeptidase Complex
  • Transcription Factors
  • Ubiquitin
  • Ubiquitin-Protein Ligases