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.
Abstract
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.
Funder
National Institutes of Health
American Heart Association
Subject
Cell Biology,Developmental Biology
Cited by
2 articles.
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