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The NEDD8 system is essential for cell cycle progression and morphogenetic pathway in mice

K Tateishi1, M Omata, K Tanaka

  • 1Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Bunkyo-Ku, Tokyo 113-8613, Japan.

The Journal of Cell Biology
|November 7, 2001
PubMed

Insights

The NEDD8 system is crucial for mammalian development, regulating cell cycle progression and protein degradation. Its absence leads to embryonic lethality and cell cycle arrest, highlighting its essential role.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Background:

  • NEDD8/Rub1 is a ubiquitin-like modifier essential for cullin (Cul) protein function.
  • Cul proteins are key components of SCF ubiquitin ligase complexes, regulating protein degradation.
  • The NEDD8 system's role in mammalian development is largely unknown.

Purpose of the Study:

  • To investigate the essential role of the NEDD8 system in mammalian development.
  • To determine the function of the Uba3 gene, encoding a catalytic subunit of the NEDD8-activating enzyme, in vivo.

Main Methods:

  • Generation of Uba3-deficient mice (Uba3(-/-)).
  • Analysis of embryonic development, cell apoptosis, and cell cycle progression in mutant embryos.
  • Assessment of protein expression, including beta-Catenin, cyclin E, and p57(Kip2).

Main Results:

  • Uba3(-/-) mice exhibited embryonic lethality at the periimplantation stage.
  • Mutant embryos showed selective inner cell mass apoptosis and trophoblastic cell cycle arrest.
  • Aberrant expression of cell cycle regulators (cyclin E, p57(Kip2)) and accumulation of beta-Catenin were observed.

Conclusions:

  • The NEDD8 system is indispensable for embryonic development, regulating both mitotic and endoreduplicative cell cycles.
  • The NEDD8 system is vital for protein degradation pathways, including those involving SCF ligases and beta-Catenin.
  • NEDD8 is essential for cell cycle progression and morphogenesis, likely via cullin-mediated pathways.

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