Control of Meiotic and Mitotic Progression by the F Box Protein β-Trcp1 In Vivo
2003; Elsevier BV; Volume: 4; Issue: 6 Linguagem: Inglês
10.1016/s1534-5807(03)00154-0
ISSN1878-1551
AutoresDaniele Guardavaccaro, Yasusei Kudo, Jérôme Boulaire, Marco Barchi, Luca Busino, Maddalena Donzelli, Florence Margottin-Goguet, Peter K. Jackson, Lili Yamasaki, Michele Pagano,
Tópico(s)Hippo pathway signaling and YAP/TAZ
ResumoSCF 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 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.
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