Thursday, February 20, 2014
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antibodies linked to the E3 ubiquitin ligase domain
of STIP1 homology and U-box containing protein 1
(STUB1; CHIP) to enable targeted
In vitro and cell culture studies suggest intracellular
expression of antibodies linked to the E3 ubiquitin ligase domain of CHIP
could promote ubiquitin-mediated degradation of target proteins. In vitro,
an E3 ubiquitin ligase domain-linked single-chain variable fragment (scFv)
specific for a model target protein caused ubiquitination of the protein. In
cultured mammalian cells, plasmid-based expression of an E3 ubiquitin ligase
domain-linked antibody-like protein led to degradation of a plasmid-expressed
protein from Escherichia coli. Next steps include developing
extracellular or transgenic delivery methods and testing the effect of the
molecules, called ubiquibodies, on disease-associated proteins in cell
GlaxoSmithKline plc and Arvinas Inc. each have discovery stage
programs to find small molecules that promote ubiquitin-mediated protein
degradation (see Degradation from within, page 10).
SciBX 7(7); doi:10.1038/scibx.2014.211
Published online Feb. 20, 2014
Patent pending; being
licensed to Ubiquizyme Inc.
Protnoff, A.D. et al. J.
Biol. Chem.; published online Jan. 28, 2014;
Contact: Matthew P. DeLisa, Cornell University, Ithaca, N.Y.
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