Copper Chaperone Atox1 Interacts with Cell Cycle Proteins

Maria Matson Dzebo; Stéphanie Blockhuys; Sebastian Valenzuela; Emanuele Celauro; Elin K Esbjörner; Pernilla Wittung-Stafshede

doi:10.1016/j.csbj.2018.10.018

Copper Chaperone Atox1 Interacts with Cell Cycle Proteins

Comput Struct Biotechnol J. 2018 Oct 31:16:443-449. doi: 10.1016/j.csbj.2018.10.018. eCollection 2018.

Authors

Maria Matson Dzebo¹, Stéphanie Blockhuys¹, Sebastian Valenzuela¹, Emanuele Celauro¹, Elin K Esbjörner¹, Pernilla Wittung-Stafshede¹

Affiliation

¹ Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden.

Abstract

The anaphase-promoting complex (APC) is involved in several processes in the cell cycle, most prominently it facilitates the separation of the sister chromatids during mitosis, before cell division. Because of the key role in the cell cycle, APC is suggested as a putative target for anticancer agents. We here show that the copper chaperone Atox1, known for shuttling copper in the cytoplasm from Ctr1 to ATP7A/B in the secretory pathway, interacts with several APC subunits. Atox1 interactions with APC subunits were discovered by mass spectrometry of co-immunoprecipitated samples and further confirmed using proximity ligation assays in HEK293T cells. Upon comparing wild-type cells with those in which the Atox1 gene had been knocked out, we found that in the absence of Atox1 protein, cells have prolonged G₂/M phases and a slower proliferation rate. Thus, in addition to copper transport for loading of copper-dependent enzymes, Atox1 may modulate the cell cycle by interacting with APC subunits.