Memo1 binds reduced copper ions, interacts with copper chaperone Atox1, and protects against copper-mediated redox activity in vitro
Artikel i vetenskaplig tidskrift, 2022

The protein mediator of ERBB2-driven cell motility 1 (Memo1) is connected to many signaling pathways that play key roles in cancer. Memo1 was recently postulated to bind copper (Cu) ions and thereby promote the generation of reactive oxygen species (ROS) in cancer cells. Since the concentration of Cu as well as ROS are increased in cancer cells, both can be toxic if not well regulated. Here, we investigated the Cu-binding capacity of Memo1 using an array of biophysical methods at reducing as well as oxidizing conditions in vitro. We find that Memo1 coordinates two reduced Cu (Cu(I)) ions per protein, and, by doing so, the metal ions are shielded from ROS generation. In support of biological relevance, we show that the cytoplasmic Cu chaperone Atox1, which delivers Cu(I) in the secretory pathway, can interact with and exchange Cu(I) with Memo1 in vitro and that the two proteins exhibit spatial proximity in breast cancer cells. Thus, Memo1 appears to act as a Cu(I) chelator (perhaps shuttling the metal ion to Atox1 and the secretory path) that protects cells from Cu-mediated toxicity, such as uncontrolled formation of ROS. This Memo1 functionality may be a safety mechanism to cope with the increased demand of Cu ions in cancer cells.

cancer

copper-binding protein

Atox1

Memo1

reactive oxygen species

Författare

Xiaolu Zhang

Chalmers, Biologi och bioteknik, Kemisk biologi

Gulshan Rameshrao Walke

Chalmers, Biologi och bioteknik, Kemisk biologi

Istvan Horvath

Chalmers, Biologi och bioteknik, Kemisk biologi

Ranjeet Kumar

Chalmers, Biologi och bioteknik, Kemisk biologi

Stephanie Blockhuys

Göteborgs universitet

Stellan Holgersson

Chalmers, Kemi och kemiteknik, Energi och material

P. H. Walton

University of York

Pernilla Wittung Stafshede

Chalmers, Biologi och bioteknik, Kemisk biologi

Proceedings of the National Academy of Sciences of the United States of America

0027-8424 (ISSN) 1091-6490 (eISSN)

Vol. 119 37 e2206905119-

Ämneskategorier

Cellbiologi

Cell- och molekylärbiologi

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

DOI

10.1073/pnas.2206905119

PubMed

36067318

Mer information

Senast uppdaterat

2023-10-26