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

被引:13
作者
Zhang, Bichao [1 ]
Binks, Tim [1 ]
Burke, Richard [1 ]
机构
[1] Monash Univ, Sch Biol Sci, Wellington Rd, Clayton, Vic 3800, Australia
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2020年 / 1867卷 / 10期
基金
英国医学研究理事会;
关键词
Slmb; beta-TrCP; E3 ubiquitin ligase; Copper; CTR1; ATP7; BETA-TRCP; TRANSPORTER; EXPRESSION; TURNOVER; COMPLEX; PIGMENTATION; DEGRADATION; MECHANISM; PROMOTES; MENKES;
D O I
10.1016/j.bbamcr.2020.118768
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Drosophila Slimb (Slmb) gene encodes a Skpl-Cull-F-box (SCP) E3 ubiquitin ligase orthologous to the human beta-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.
引用
收藏
页数:13
相关论文
共 58 条
  • [1] Asada S, 2008, INT J MOL MED, V22, P95
  • [2] Copper homeostasis in Drosophila by complex interplay of import, storage and behavioral avoidance
    Balamurugan, Kuppusamy
    Egli, Dieter
    Hua, Haiqing
    Rajaram, Rama
    Seisenbacher, Gerhard
    Georgiev, Oleg
    Schaffner, Walter
    [J]. EMBO JOURNAL, 2007, 26 (04) : 1035 - 1044
  • [3] Tissue-specific interplay between copper uptake and efflux in Drosophila
    Binks, Tim
    Lye, Jessica Charlotte
    Camakaris, James
    Burke, Richard
    [J]. JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, 2010, 15 (04): : 621 - 628
  • [4] Expression and localisation of the essential copper transporter DmATP7 in Drosophila neuronal and intestinal tissues
    Burke, Richard
    Commons, Elizabeth
    Camakaris, James
    [J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2008, 40 (09) : 1850 - 1860
  • [5] Drosophila melanogaster Models of Metal-Related Human Diseases and Metal Toxicity
    Calap-Quintana, Pablo
    Gonzalez-Fernandez, Javier
    Sebastia-Ortega, Noelia
    Vicente Llorens, Jose
    Dolores Molto, Maria
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2017, 18 (07)
  • [6] Cheng R., 2018, BIOCH BIOPHYS ACTA G, P2271
  • [7] Clustering and Negative Feedback by Endocytosis in Planar Cell Polarity Signaling Is Modulated by Ubiquitinylation of Prickle
    Cho, Bomsoo
    Pierre-Louis, Gandhy
    Sagner, Andreas
    Eaton, Suzanne
    Axelrod, Jeffrey D.
    [J]. PLOS GENETICS, 2015, 11 (05):
  • [8] Cis-regulatory elements in the Accord retrotransposon result in tissue-specific expression of the Drosophila melanogaster insecticide resistance gene Cyp6g1
    Chung, Henry
    Bogwitz, Michael R.
    McCart, Caroline
    Andrianopoulos, Alex
    ffrench-Constant, Richard H.
    Batterham, Philip
    Daborn, Phillip J.
    [J]. GENETICS, 2007, 175 (03) : 1071 - 1077
  • [9] Dynamic internalization and recycling of a metal ion transporter: Cu homeostasis and CTR1, the human Cu+ uptake system
    Clifford, Rebecca J.
    Maryon, Edward B.
    Kaplan, Jack H.
    [J]. JOURNAL OF CELL SCIENCE, 2016, 129 (08) : 1711 - 1721
  • [10] The drosophila Bcl-2 family protein Debcl is targeted to the proteasome by the β-TrCP homologue slimb
    Colin, Jessie
    Garibal, Julie
    Clavier, Amandine
    Rincheval-Arnold, Aurore
    Gaumer, Sebastien
    Mignotte, Bernard
    Guenal, Isabelle
    [J]. APOPTOSIS, 2014, 19 (10) : 1444 - 1456