Haploinsufficient tumor suppressor Tip60 negatively regulates oncogenic Aurora B kinase
Date
2019-12
Journal Title
Journal ISSN
Volume Title
Publisher
Indian Academy of Sciences
Abstract
The Aurora kinases represent a group of serine/threonine kinases which are crucial regulators of mitosis. DysregulatedAurora kinase B (AurkB) expression, stemming from genomic amplification, increased gene transcription or overexpressionof its allosteric activators, is capable of initiating and sustaining malignant phenotypes. Although AurkB level in cells iswell-orchestrated, studies that relate to its stability or activity, independent of mitosis, are lacking. We report that AurkBundergoes acetylation in vitro by lysine acetyltransferases (KATs) belonging to different families, namely by p300 andTip60. The haploinsufficient tumor suppressor Tip60 acetylates two highly conserved lysine residues within the kinasedomain of AurkB which not only impinges the protein stability but also its kinase activity. These results signify a probableoutcome on the increase in ‘‘overall activity’’ of AurkB upon Tip60 downregulation, as observed under cancerous conditions. The present work, therefore, uncovers an important functional interplay between AurkB and Tip60, frailty of whichmay be an initial event in carcinogenesis.
Description
Keywords
AurkB, acetylation, kinase activity, stability, Tip60
Citation
Bose Arnab, Sudevan Surabhi, Rao Vinay J, Shima Hiroki, Trivedi Arun Kumar, Igarashi Kazuhiko, Kundu Tapas K. Haploinsufficient tumor suppressor Tip60 negatively regulates oncogenic Aurora B kinase. Journal of Biosciences. 2019 Dec; 44(6): 1-8