The role of RING box protein 1 in mouse oocyte meiotic maturation

PLoS One. 2013 Jul 11;8(7):e68964. doi: 10.1371/journal.pone.0068964. Print 2013.

Abstract

RING box protein-1 (RBX1) is an essential component of Skp1-cullin-F-box protein (SCF) E3 ubiquitin ligase and participates in diverse cellular processes by targeting various substrates for degradation. However, the physiological function of RBX1 in mouse oocyte maturation remains unknown. Here, we examined the expression, localization and function of RBX1 during mouse oocyte meiotic maturation. Immunofluorescence analysis showed that RBX1 displayed dynamic distribution during the maturation process: it localized around and migrated along with the spindle and condensed chromosomes. Rbx1 knockdown with the appropriate siRNAs led to a decreased rate of first polar body extrusion and most oocytes were arrested at metaphase I. Moreover, downregulation of Rbx1 caused accumulation of Emi1, an inhibitor of the anaphase-promoting complex/cyclosome (APC/C), which is required for mouse meiotic maturation. In addition, we found apparently increased expression of the homologue disjunction-associated protein securin and cyclin B1, which are substrates of APC/C E3 ligase and need to be degraded for meiotic progression. These results indicate the essential role of the SCF(βTrCP)-EMI1-APC/C axis in mouse oocyte meiotic maturation. In conclusion, we provide evidence for the indispensable role of RBX1 in mouse oocyte meiotic maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Chromosomes
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism
  • Down-Regulation
  • Female
  • Meiosis / genetics
  • Meiosis / physiology*
  • Metaphase / genetics
  • Mice
  • Mice, Inbred ICR
  • Oocytes / metabolism
  • Oocytes / physiology*
  • Proteins / genetics
  • Proteins / metabolism
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Securin / genetics
  • Securin / metabolism
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / physiology
  • Ubiquitin-Protein Ligase Complexes / genetics
  • Ubiquitin-Protein Ligase Complexes / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Carrier Proteins
  • Ccnb1 protein, mouse
  • Cyclin B1
  • Emi1 protein, mouse
  • PTTG1 protein, mouse
  • Proteins
  • RBX1 protein, mouse
  • Securin
  • Ubiquitin-Protein Ligase Complexes
  • SKP Cullin F-Box Protein Ligases
  • Ubiquitin-Protein Ligases

Grants and funding

This work was supported by grants from the National Basic Research Program of China 973 Program) (No. 2012CB944704 (http://www.973.gov.cn/AreaAppl.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.