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

Saili Moghe1, Fei Jiang, Yoshie Miura

  • 1Eppley Institute for Research in Cancer and Allied Diseases, 987696 Nebraska Medical Center, University of Nebraska Medical Center , Omaha, NE 68198-7696 , USA.

Biology Open
|December 6, 2012
PubMed

Insights

The CUL3-KLHL18 ubiquitin ligase complex is crucial for timely cell division by regulating Aurora-A kinase activity. This discovery clarifies a key pathway controlling mitotic entry.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Ubiquitin ligases regulate protein degradation and cellular functions.
  • The cullin-RING (CRL) family, including CUL3, plays vital roles in cell cycle control.
  • BTB proteins act as substrate adaptors for CUL3 ligases.

Purpose of the Study:

  • To investigate the role of the CUL3-KLHL18 complex in regulating cell cycle progression.
  • To determine the mechanism by which CUL3-KLHL18 influences mitotic entry.
  • To identify substrates and interacting partners of the CUL3-KLHL18 ligase.

Main Methods:

  • RNA interference (RNAi) to deplete CUL3 and KLHL18.
  • Immunoprecipitation to identify interacting proteins.
  • In vitro ubiquitylation assays.
  • Western blotting to assess protein levels and modifications.

Main Results:

  • Depletion of CUL3 and KLHL18 delays mitotic entry and centrosomal Aurora-A activation.
  • Aurora-A kinase was identified as a KLHL18-interacting partner.
  • CUL3-KLHL18 ligase promotes Aurora-A ubiquitylation in vivo and in vitro.

Conclusions:

  • The CUL3-KLHL18 ubiquitin ligase complex is essential for timely mitotic entry.
  • This ligase regulates the activation of Aurora-A kinase at centrosomes.
  • The CUL3-KLHL18 ligase controls mitotic progression via an Aurora-A-dependent pathway.
Keywords:
Aurora-ABTBCUL3POZmitotic entryubiquitin

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