The E3 ubiquitin ligase Slimb/β-TrCP is required for normal copper homeostasis in Drosophila

Bichao Zhang, Tim Binks, Richard Burke

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

The Drosophila Slimb (Slmb) gene encodes a Skp1-Cul1-F-box (SCP) E3 ubiquitin ligase orthologous to the human β-TrCP/BTRC protein. Slmb and/or BTRC play regulatory roles in numerous biological processes by ubiquitinating several substrate proteins which are then targeted for proteasomal degradation. Here, we demonstrate an additional role for Slmb in maintaining cellular copper homeostasis. In the thorax, midgut and eye, Slmb knockdown causes copper deficiency phenotypes which can be rescued by increasing cellular copper levels via decreased efflux or increased uptake. Furthermore, Slmb knockdown results in decreased levels of the copper transporters Ctr1A and ATP7, indicating Slmb is required to regulate copper homeostasis. We also present evidence that the transcription factor Cap-n-Collar (Nrf2 in mammals), a known substrate of Slmb/BTRC, mediates Slmb's regulatory effect on Ctr1A in a post-transcriptional manner.

Original languageEnglish
Article number118768
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1867
Issue number10
DOIs
Publication statusPublished - Oct 2020

Keywords

  • ATP7
  • Copper
  • CTR1
  • E3 ubiquitin ligase
  • Slmb
  • β-TrCP

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