AUTHOR=Britigan Eric M. C. , Wan Jun , Sam Daniel K. , Copeland Sarah E. , Lasek Amber L. , Hrycyniak Laura C. F. , Wang Lei , Audhya Anjon , Burkard Mark E. , Roopra Avtar , Weaver Beth A. 

TITLE=Increased Aurora B expression reduces substrate phosphorylation and induces chromosomal instability

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.1018161

DOI=10.3389/fcell.2022.1018161

ISSN=2296-634X

ABSTRACT=<p>Increased Aurora B protein expression, which is common in cancers, is expected to increase Aurora B kinase activity, yielding elevated phosphorylation of Aurora B substrates. In contrast, here we show that elevated expression of Aurora B reduces phosphorylation of six different Aurora B substrates across three species and causes defects consistent with Aurora B inhibition. Complexes of Aurora B and its binding partner INCENP autophosphorylate in trans to achieve full Aurora B activation. Increased expression of Aurora B mislocalizes INCENP, reducing the local concentration of Aurora B:INCENP complexes at the inner centromere/kinetochore. Co-expression of INCENP rescues Aurora B kinase activity and mitotic defects caused by elevated Aurora B. However, INCENP expression is not elevated in concert with Aurora B in breast cancer, and increased expression of Aurora B causes resistance rather than hypersensitivity to Aurora B inhibitors. Thus, increased Aurora B expression reduces, rather than increases, Aurora B kinase activity.</p>