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Increased Aurora B expression reduces substrate phosphorylation and induces chromosomal instability
Journal article   Open access   Peer reviewed

Increased Aurora B expression reduces substrate phosphorylation and induces chromosomal instability

Eric M. C. Britigan, Jun Wan, Daniel K. Sam, Sarah E. Copeland, Amber L. Lasek, Laura C. F. Hrycyniak, Lei Wang, Anjon Audhya, Mark E. Burkard, Avtar Roopra, …
Frontiers in cell and developmental biology, Vol.10, pp.1018161-1018161
10/13/2022
DOI: 10.3389/fcell.2022.1018161
PMCID: PMC9606593
PMID: 36313574
url
https://doi.org/10.3389/fcell.2022.1018161View
Published (Version of record) Open Access

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.
 Cell and Developmental Biology

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