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Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo.

SCF ubiquitin ligases, composed of three major subunits, Skp1, Cul1, and one of many F box proteins (Fbps), control the proteolysis of important cellular regulators. We have inactivated the gene encoding the Fbp beta-Trcp1 in mice. beta-Trcp1(-/-) males show reduced fertility correlating with an accumulation of methaphase I spermatocytes. beta-Trcp1(-/-) MEFs display a lengthened mitosis, centrosome overduplication, multipolar metaphase spindles, and misaligned chromosomes. Furthermore, cyclin A, cyclin B, and Emi1, an inhibitor of the anaphase promoting complex, are stabilized in mitotic beta-Trcp1(-/-) MEFs. Indeed, we demonstrate that Emi1 is a bona fide substrate of beta-Trcp1. In contrast, stabilization of beta-catenin and IkappaBalpha, two previously reported beta-Trcp1 substrates, does not occur in the absence of beta-Trcp1 and instead requires the additional silencing of beta-Trcp2 by siRNA. Thus, beta-Trcp1 regulates the timely order of meiotic and mitotic events.

Pubmed ID: 12791266

Authors

  • Guardavaccaro D
  • Kudo Y
  • Boulaire J
  • Barchi M
  • Busino L
  • Donzelli M
  • Margottin-Goguet F
  • Jackson PK
  • Yamasaki L
  • Pagano M

Journal

Developmental cell

Publication Data

June 6, 2003

Associated Grants

  • Agency: NCI NIH HHS, Id: R01-CA76584
  • Agency: NCI NIH HHS, Id: R01-CA79646
  • Agency: NIGMS NIH HHS, Id: R01-GM57587

Mesh Terms

  • Animals
  • Cell Cycle Proteins
  • Centrosome
  • Cyclin A
  • Cyclin B
  • GTP-Binding Proteins
  • Gene Expression Regulation
  • Genotype
  • Infertility, Male
  • Male
  • Meiosis
  • Mice
  • Mice, Knockout
  • Mitosis
  • Oxidoreductases
  • Phenotype
  • Proteins
  • Spermatocytes
  • Substrate Specificity
  • beta-Transducin Repeat-Containing Proteins