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

Daniele Guardavaccaro, Yasusei Kudo, Jérôme Boulaire, Marco Barchi, Luca Busino, Maddalena Donzelli, Florence Margottin-Goguet, Peter K. Jackson, Lili Yamasaki, Michele Pagano

Research output: Contribution to journalArticle

Abstract

SCF ubiquitin ligases, composed of three major subunits, S kp1, C ul1, and one of many F box p roteins (Fbps), control the proteolysis of important cellular regulators. We have inactivated the gene encoding the Fbp β-Trcp1 in mice. β-Trcp1-/- males show reduced fertility correlating with an accumulation of methaphase I spermatocytes. β-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 β-Trcp1-/- MEFs. Indeed, we demonstrate that Emi1 is a bona fide substrate of β-Trcp1. In contrast, stabilization of β-catenin and IκBα, two previously reported β-Trcp1 substrates, does not occur in the absence of β-Trcp1 and instead requires the additional silencing of β-Trcp2 by siRNA. Thus, β-Trcp1 regulates the timely order of meiotic and mitotic events.

Original languageEnglish
Pages (from-to)799-812
Number of pages14
JournalDevelopmental Cell
Volume4
Issue number6
DOIs
Publication statusPublished - Jun 1 2003

ASJC Scopus subject areas

  • Developmental Biology

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    Guardavaccaro, D., Kudo, Y., Boulaire, J., Barchi, M., Busino, L., Donzelli, M., Margottin-Goguet, F., Jackson, P. K., Yamasaki, L., & Pagano, M. (2003). Control of meiotic and mitotic progression by the F box protein β-Trcp1 in vivo. Developmental Cell, 4(6), 799-812. https://doi.org/10.1016/S1534-5807(03)00154-0