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 کاملRequirement of the SCF ubiquitin ligase for degradation of the fission yeast S-phase cyclin Cig2
Present address: =Cell Cycle Control Group, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, UK. ^Nomura Research & Advisory Co. Ltd., Urbannet Otemachi Building 2-2-2, Otemachi, Chiyoda-ku, Tokyo100-8130, JAPAN. +Center for Gene Science, Hiroshima University, 1-4-2 Kagamiyama, Higashi-Hiroshima 739-8537, Japan. ~Analytical Research Centre for Experimental Sciences, Saga Univer...
متن کاملStructural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase.
The ubiquitin-mediated proteolysis of the Cdk2 inhibitor p27(Kip1) plays a central role in cell cycle progression, and enhanced degradation of p27(Kip1) is associated with many common cancers. Proteolysis of p27(Kip1) is triggered by Thr187 phosphorylation, which leads to the binding of the SCF(Skp2) (Skp1-Cul1-Rbx1-Skp2) ubiquitin ligase complex. Unlike other known SCF substrates, p27(Kip1) ub...
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ژورنال
عنوان ژورنال: Molecular Cell
سال: 2002
ISSN: 1097-2765
DOI: 10.1016/s1097-2765(02)00538-5