The E3 ligase CUL3/RDX controls centromere maintenance by ubiquitylating and stabilizing CENP-A in a CAL1-dependent manner

• Verfasst von: Bade, Debora [VerfasserIn]
• Verfasst von: Pauleau, Anne-Laure [VerfasserIn]
• Verfasst von: Wendler, Astrid [VerfasserIn]
• Verfasst von: Erhardt, Sylvia [VerfasserIn]
• Titel: The E3 ligase CUL3/RDX controls centromere maintenance by ubiquitylating and stabilizing CENP-A in a CAL1-dependent manner
• Verf.angabe: Debora Bade, Anne-Laure Pauleau, Astrid Wendler, and Sylvia Erhardt
• E-Jahr: 2014
• Jahr: March 10, 2014
• Umfang: 12 S.
• Fussnoten: Gesehen am 15.08.2017
• Titel Quelle: Enthalten in: Developmental cell
• Ort Quelle: Cambridge, Mass. : Cell Press, 2001
• Jahr Quelle: 2014
• Band/Heft Quelle: 28(2014), 5, Seite 508-519
• ISSN Quelle: 1878-1551
• DOI: doi:10.1016/j.devcel.2014.01.031
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1562450980

Abstract

Centromeres are defined by the presence of the histone H3 variant CENP-A in a subset of centromeric nucleosomes. CENP-A deposition to centromeres depends on a specialized loading factor from yeast to humans that is called CAL1 in Drosophila. Here, we show that CAL1 directly interacts with RDX, an adaptor for CUL3-mediated ubiquitylation. However, CAL1 is not a substrate of the CUL3/RDX ligase but functions as an additional substrate-specifying factor for the CUL3/RDX-mediated ubiquitylation of CENP-A. Remarkably, ubiquitylation of CENP-A by CUL3/RDX does not trigger its degradation but stabilizes CENP-A and CAL1. Loss of RDX leads to a rapid degradation of CAL1 and CENP-A and to massive chromosome segregation defects during development. Essentially, we identified a proteolysis-independent role of ubiquitin conjugation in centromere regulation that is essential for the maintenance of the centromere-defining protein CENP-A and its loading factor CAL1.