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The E3 ubiquitin ligase Slimb/β-TrCP is required for normal copper homeostasis in Drosophila.
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 5.1 ) Pub Date : 2020-06-02 , DOI: 10.1016/j.bbamcr.2020.118768
Bichao Zhang 1 , Tim Binks 1 , Richard Burke 1
Affiliation  

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.



中文翻译:

果蝇正常的铜稳态需要E3泛素连接酶Slimb /β-TrCP。

果蝇SlimbSlmb)基因编码SKP1-CUL1-F-盒(SCP)E3泛素连接酶的直系同源人类β-TRCP / BTRC蛋白。S1mb和/或BTRC通过泛素化几种底物蛋白而在许多生物学过程中起调节作用,然后将这些底物蛋白靶向用于蛋白酶体降解。在这里,我们证明了Slmb在维持细胞铜稳态中的额外作用。在胸,中肠和眼中,Slbb敲低会引起铜缺乏症表型,可通过减少细胞外排或增加摄取来增加细胞内铜水平来挽救铜缺乏症。此外,Slmb敲低导致铜转运蛋白Ctr1A和ATP7的水平降低,表明需要Slmb来调节铜稳态。我们还提供证据表明,转录因子Cap-n-Collar(在哺乳动物中为Nrf2)是Slmb / BTRC的已知底物,以转录后的方式介导Slmb对Ctr1A的调节作用。

更新日期:2020-06-02
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