Haploinsufficient tumor suppressor Tip60 negatively regulates oncogenic Aurora B kinase

Arnab Bose, Surabhi Sudevan, Vinay J. Rao, Hiroki Shima, Arun Kumar Trivedi, Kazuhiko Igarashi, Tapas K. Kundu

Research output: Contribution to journalArticle

Abstract

The Aurora kinases represent a group of serine/threonine kinases which are crucial regulators of mitosis. Dysregulated Aurora kinase B (AurkB) expression, stemming from genomic amplification, increased gene transcription or overexpression of its allosteric activators, is capable of initiating and sustaining malignant phenotypes. Although AurkB level in cells is well-orchestrated, studies that relate to its stability or activity, independent of mitosis, are lacking. We report that AurkB undergoes acetylation in vitro by lysine acetyltransferases (KATs) belonging to different families, namely by p300 and Tip60. The haploinsufficient tumor suppressor Tip60 acetylates two highly conserved lysine residues within the kinase domain of AurkB which not only impinges the protein stability but also its kinase activity. These results signify a probable outcome 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 which may be an initial event in carcinogenesis.

Original languageEnglish
Article number147
JournalJournal of Biosciences
Volume44
Issue number6
DOIs
Publication statusPublished - 2019 Dec 1

Keywords

  • AurkB
  • Tip60
  • acetylation
  • kinase activity
  • stability

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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