منابع مشابه
Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation.
Conjugation of ubiquitin-like protein Nedd8 to cullins (neddylation) is essential for the function of cullin-RING ubiquitin ligases (CRLs). Here, we show that neddylation stimulates CRL activity by multiple mechanisms. For the initiator ubiquitin, the major effect is to bridge the approximately 50 A gap between naked substrate and E2 approximately Ub bound to SCF. The gap between the acceptor l...
متن کامل[42] Druggability of SCF Ubiquitin Ligase–Protein Interfaces
The unique mechanism of the SCF ubiquitin ligase poses a challenge to drug discovery. A central enzymatic small molecule–binding active site is not evident in this multisubunit protein enzyme, as is the case with kinases or proteases. Instead, the SCF ligase seems to accomplish ubiquitylation through a series of cooperative movements dependent on the protein interfaces between its components an...
متن کاملOccurrence of a putative SCF ubiquitin ligase complex in Drosophila.
Many proteins are targeted to proteasome degradation by a family of E3 ubiquitin ligases, termed SCF complexes, that link substrate proteins to an E2 ubiquitin-conjugating enzyme. SCFs are composed of three core proteins-Skp1, Cdc53/Cull, Rbx1/Hrt1-and a substrate specific F-box protein. We have identified in Drosophila melanogaster the closest homologues to the human components of the SCF(beta...
متن کاملOskar Is Targeted for Degradation by the Sequential Action of Par-1, GSK-3, and the SCF-Slimb Ubiquitin Ligase
Translation of oskar messenger RNA (mRNA) is activated at the posterior of the Drosophila oocyte, producing Long Oskar, which anchors the RNA, and Short Oskar, which nucleates the pole plasm, containing the posterior and germline determinants. Here, we show that Oskar is phosphorylated by Par-1 and GSK-3/Shaggy to create a phosphodegron that recruits the SCF(-Slimb) ubiquitin ligase, which targ...
متن کاملNanobody-targeted E3-ubiquitin ligase complex degrades nuclear proteins
Targeted protein degradation is a powerful tool in determining the function of specific proteins or protein complexes. We fused nanobodies to SPOP, an adaptor protein of the Cullin-RING E3 ubiquitin ligase complex, resulting in rapid ubiquitination and subsequent proteasome-dependent degradation of specific nuclear proteins in mammalian cells and zebrafish embryos. This approach is easily modif...
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ژورنال
عنوان ژورنال: Nature Reviews Drug Discovery
سال: 2014
ISSN: 1474-1776,1474-1784
DOI: 10.1038/nrd4432