Memo1 binds reduced copper ions, interacts with copper chaperone Atox1, and protects against copper-mediated redox activity invitro

Zhang, Xiaolu, 1983 (author): Chalmers tekniska högskola,Chalmers University of Technology

Walke, Gulshan Rameshrao, 1986 (author): Chalmers tekniska högskola,Chalmers University of Technology

Horvath, Istvan, 1979 (author): Chalmers tekniska högskola,Chalmers University of Technology

Kumar, Ranjeet, 1980 (author): Chalmers tekniska högskola,Chalmers University of Technology

Blockhuys, Stéphanie, 1983 (author): Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery,University of Gothenburg

Holgersson, Stellan, 1964 (author): Chalmers tekniska högskola,Chalmers University of Technology

Wittung Stafshede, Pernilla, 1968 (author): Chalmers tekniska högskola,Chalmers University of Technology

(creator_code:org_t)

2022-09-06
2022
English.
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 119:37

Related links:: https://research.cha... (primary) (free); show more...; https://gup.ub.gu.se...; https://doi.org/10.1...; https://research.cha...; show less...

Abstract Subject headings

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 invitro. 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 invitro 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.

NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

By the author/editor: Zhang, Xiaolu, 1 ...; Walke, Gulshan R ...; Horvath, Istvan, ...; Kumar, Ranjeet, ...; Blockhuys, Stéph ...; Holgersson, Stel ...; show more...; Walton, P. H.; Wittung Stafshed ...; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Cell Biology

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

By the university: University of Gothenburg; Chalmers University of Technology

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