Investigating PRMT6 Protein Interactions in Breast Cancer Cells

Abstract

Breast cancer remains the most diagnosed cancer in women and a leading cause of death attributed to refractory tumours unresponsive to chemotherapeutics. Understanding breast cancer etiology and the molecular landscape contributing to chemoresistance is crucial for developing a novel treatment strategy in tumours to increase the chemotherapy response. PRMT6 is a type-I PRMT enzyme that catalyzes methylarginine post-translational modifications critical to the cell’s physiological processes. PRMT6 has aberrant expression detected in breast cancer potentially contributing to poor prognosis. Our lab has previously observed a role for PRMT6 in mediating stress granule formation, which could represent a chemoresistance mechanism used by breast cancer cells. This study attempts to investigate the unknown PRMT6 molecular mechanism promoting bortezomib chemoresistance by identifying novel PRMT6 protein interactors or substrates that help govern these molecular functions. We engineered BirA-PRMT6 expressing BioID cells and found PRMT6 to interact with ADAR1 p110 in the nucleus of breast cancer cells. The ADAR1 p110 and PRMT6 interaction is not impacted by bortezomib treatment indicating a potential alternative form of regulation. Lastly, PRMT6 does not regulate the ADAR1 p150 isoform through N-terminal arginine methylation, however, ADAR1 p110 is not eliminated as a potential PRMT6 substrate involved in the regulation of the stress response.