Lin Chen, Na Li, Meiqi Zhang, Mingming Sun, Jiaxuan Bian, Bo Yang, Zhengcunxiao Li, Jiayu Wang, Fei Li, Xiaomeng Shi, Yuan Wang, Feng Yuan, Peng Zou, Changliang Shan, Jing Wang
Mammalian cell nuclei contain copper, and cancer cells are known to accumulate aberrantly high copper levels, yet the mechanisms underlying nuclear accumulation and copper's broader functional significance remain poorly understood. Here, by combining APEX2-based proximity labeling focused on the copper chaperone Atox1 with mass spectrometry we identified a previously unrecognized nuclear copper binding protein, Cysteine-rich protein 2 (CRIP2), that interacts with Atox1 in the nucleus. We show that Atox1 transfers copper to CRIP2, which induces a change in CRIP2's secondary structure that ultimately promotes its ubiquitin-mediated proteasomal degradation...
September 22, 2021: Angewandte Chemie