SCF ubiquitin ligases, composed of three major sub- units, 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 -Trcp1 in mice. -Trcp1/ males show reduced fer- tility correlating with an accumulation of methaphase I spermatocytes. -Trcp1/ MEFs display a lengthened mitosis, centrosome overduplication, multipolar meta- phase spindles, and misaligned chromosomes. Fur- thermore, cyclin A, cyclin B, and Emi1, an inhibitor of the anaphase promoting complex, are stabilized in mitotic -Trcp1/ MEFs. Indeed, we demonstrate that Emi1 is a bona fide substrate of -Trcp1. In contrast, stabilization of -catenin and IB, two previously re- ported -Trcp1 substrates, does not occur in the ab- sence of -Trcp1 and instead requires the additional silencing of -Trcp2 by siRNA. Thus, -Trcp1 regulates the timely order of meiotic and mitotic events.

Control of Meiotic and Mitotic Progression by the F Box Protein β-Trcp1 In Vivo

Guardavaccaro, Daniele;
2003-01-01

Abstract

SCF ubiquitin ligases, composed of three major sub- units, 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 -Trcp1 in mice. -Trcp1/ males show reduced fer- tility correlating with an accumulation of methaphase I spermatocytes. -Trcp1/ MEFs display a lengthened mitosis, centrosome overduplication, multipolar meta- phase spindles, and misaligned chromosomes. Fur- thermore, cyclin A, cyclin B, and Emi1, an inhibitor of the anaphase promoting complex, are stabilized in mitotic -Trcp1/ MEFs. Indeed, we demonstrate that Emi1 is a bona fide substrate of -Trcp1. In contrast, stabilization of -catenin and IB, two previously re- ported -Trcp1 substrates, does not occur in the ab- sence of -Trcp1 and instead requires the additional silencing of -Trcp2 by siRNA. Thus, -Trcp1 regulates the timely order of meiotic and mitotic events.
2003
ubiquitin
File in questo prodotto:
File Dimensione Formato  
Guardavaccaro Dev Cell 2003.pdf

accesso aperto

Tipologia: Versione dell'editore
Licenza: Dominio pubblico
Dimensione 803.44 kB
Formato Adobe PDF
803.44 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/992898
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 322
  • ???jsp.display-item.citation.isi??? 310
social impact