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PMID:12791266

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Citation

Guardavaccaro, D, Kudo, Y, Boulaire, J, Barchi, M, Busino, L, Donzelli, M, Margottin-Goguet, F, Jackson, PK, Yamasaki, L and Pagano, M (2003) Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo. Dev. Cell 4:799-812

Abstract

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.

Links

PubMed

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:FBW1A

acts_upstream_of_or_within

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3055737

P

Seeded From UniProt

complete


See also

References

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