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A Tunable Brake for HECT Ubiquitin Ligases.

Mol Cell. 2017; 
Chen Z, Jiang H, Xu W, Li X, Dempsey DR, Zhang X, Devreotes P, Wolberger C, Amzel LM, Gabelli SB, Cole PA.
Products/Services Used Details Operation
Custom DNA/RNA Oligos e1–e6, May 4, 2017 e2 Continued REAGENT or RESOURCE Experimental Models: Cell Lines HeLa cell Oligonucleotides SOURCE ATCC Primers used in this study, see Table S1 This paper IDENTIFIER ATCC CCL-2 N/A Recombinant DNA WWP1 cDNA PTEN cDNA OCT4 cDNA NEDD4 cDNA OCT4 cDNA Software and Algorithms HKL-2000 COOT Prism 6 Genscript Cat# OHu14139 Miho Ijima, Johns Hopkins University N/A Aasen et al.... Human WWP1 cDNA was purchased from Genscript, and subcloned into pGEX6p-2. Get A Quote

摘要

The HECT E3 ligases ubiquitinate numerous transcription factors and signaling molecules, and their activity must be tightly controlled to prevent cancer, immune disorders, and other diseases. In this study, we have found unexpectedly that peptide linkers tethering WW domains in several HECT family members are key regulatory elements of their catalytic activities. Biochemical, structural, and cellular analyses have revealed that the linkers can lock the HECT domain in an inactive conformation and block the proposed allosteric ubiquitin binding site. Such linker-mediated autoinhibition of the HECT domain can be relieved by linker post-translational modifications, but complete removal of the brake can induce hyper... More

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