Control of Meiotic and Mitotic Progression by the F Box Protein β-Trcp1 In Vivo
Copyright policy )Control of Meiotic and Mitotic Progression by the F Box Protein β-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.
- University of Rome Tor Vergata Italy
- Istituti di Ricovero e Cura a Carattere Scientifico Italy
- King’s University United States
- Columbia University United States
- Stanford University United States
Male, Genotype, Mitosis, Cell Cycle Proteins, Cyclin A, Cyclin B, Substrate Specificity, Mice, GTP-Binding Proteins, Spermatocytes, ubiquitin, Animals, Settore BIO/10 - BIOCHIMICA, Trcp1, Infertility, Male, Settore BIO/16 - ANATOMIA UMANA, Centrosome, Mice, Knockout, Proteins, beta-Transducin Repeat-Containing Proteins, spermatogenesis, Meiosis, Phenotype, Gene Expression Regulation, Trcp1, spermatogenesis, Oxidoreductases, Developmental Biology
Male, Genotype, Mitosis, Cell Cycle Proteins, Cyclin A, Cyclin B, Substrate Specificity, Mice, GTP-Binding Proteins, Spermatocytes, ubiquitin, Animals, Settore BIO/10 - BIOCHIMICA, Trcp1, Infertility, Male, Settore BIO/16 - ANATOMIA UMANA, Centrosome, Mice, Knockout, Proteins, beta-Transducin Repeat-Containing Proteins, spermatogenesis, Meiosis, Phenotype, Gene Expression Regulation, Trcp1, spermatogenesis, Oxidoreductases, Developmental Biology
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