The CUL3-KLHL18 ligase regulates mitotic entry and ubiquitylates Aurora-A

Saili Moghe, Fei Jiang, Yoshie Miura, Ronald L. Cerny, Ming Ying Tsai, Manabu Furukawa

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The cullin-RING family of ubiquitin ligases regulates diverse cellular functions, such as cell cycle control, via ubiquitylation of specific substrates. CUL3 targets its substrates through BTB proteins. Here we show that depletion of CUL3 and the BTB protein KLHL18 causes a delay in mitotic entry. Centrosomal activation of Aurora-A, a kinase whose activity is required for entry into mitosis, is also delayed in depleted cells. Moreover, we identify Aurora-A as a KLHL18-interacting partner. Overexpression of KLHL18 and CUL3 promotes Aurora-A ubiquitylation in vivo, and the CUL3-KLHL18-ROC1 ligase ubiquitylates Aurora-A in vitro. Our study reveals that the CUL3-KLHL18 ligase is required for timely entry into mitosis, as well as for the activation of Aurora-A at centrosomes. We propose that the CUL3-KLHL18 ligase regulates mitotic entry through an Aurora-A-dependent pathway.

Original languageEnglish (US)
Pages (from-to)82-91
Number of pages10
JournalBiology Open
Volume1
Issue number2
DOIs
StatePublished - Feb 15 2012

Keywords

  • Aurora-A
  • BTB
  • CUL3
  • Mitotic entry
  • POZ
  • Ubiquitin

ASJC Scopus subject areas

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

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