Bcl2l10, a new Tpx2 binding partner, is a master regulator of Aurora kinase A in mouse oocytes

Cell Cycle. 2016 Dec;15(23):3296-3305. doi: 10.1080/15384101.2016.1243630. Epub 2016 Oct 18.

Abstract

Previously, we demonstrated that Bcl-2-like 10 (Bcl2l10) is associated with meiotic spindle assembly and that the gene that is most strongly down-regulated by Bcl2l10 RNAi is targeting protein for Xklp2 (Tpx2). Tpx2 is a well-known cofactor that controls the activity and localization of Aurora kinase A (Aurka) during mitotic spindle assembly. Therefore, this study was conducted (1) to identify the associations among Bcl2l10, Tpx2, and Aurka and (2) to understand how Bcl2l10 regulates meiotic spindle assembly in mouse oocytes. Bcl2l10, Tpx2, and Aurka co-localized on the meiotic spindles, and Bcl2l10 was present in the same complex with Tpx2. Tpx2 and Aurka expression decreased whereas phospho-Aurka increased in Bcl2l10 RNAi-treated oocytes. Counterbalancing changes in the levels of these 2 activators, Tpx2 and phospho-Aurka, resulted in decreased Aurka catalytic activity after Bcl2l10 RNAi treatment. Bcl2l10 RNAi decreased the expression of microtubule organizing center (MTOC)-related proteins, disturbed MTOC formation and disrupted meiotic spindle assembly. Our data demonstrate that Bcl2l10 is a binding partner of Tpx2 and a new regulator of the complex controlling the organization of microtubules and MTOC biogenesis in meiotic spindle assembly. The discovery of Bcl2l10 as a new effector of Aurka suggests that Bcl2l10 may have diverse functions in mitotic cells.

Keywords: Aurka; Bcl2l10; MTOC; Tpx2; mouse oocyte maturation.

MeSH terms

  • Animals
  • Aurora Kinase A / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Cell Differentiation
  • Female
  • HEK293 Cells
  • Humans
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism*
  • Microtubule-Organizing Center / metabolism
  • Models, Biological
  • Nuclear Proteins / metabolism*
  • Oocytes / cytology
  • Oocytes / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Transport
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA Interference
  • Spindle Apparatus / metabolism

Substances

  • BCL2-like 10 protein
  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • TPX2 protein, mouse
  • Aurora Kinase A