Targeted Degradation

Pathogen-sourced enzyme redirected

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Science  07 Jun 2019:
Vol. 364, Issue 6444, pp. 967-968
DOI: 10.1126/science.364.6444.967-e

Confocal microscopy image of fluorescent protein targets expressed in HEK293T cells

PHOTO: M. B. LUDWICKI ET AL., ACS CENT. SCI. 5, 852 (2019)

Cells of all types have the means to degrade specific proteins. These pathways can be hijacked by some bacteria to diminish host immune responses. The enzymes involved can in turn be used in the lab to modulate the proteome of eukaryotic cells. Ludwicki et al. attached a bacterial ubiquitin ligase to a protein that binds green fluorescent protein (GFP), thus redirecting it to add ubiquitin to GFP and GFP fusion proteins, which causes their degradation. The authors used polyamines and mRNA-binding proteins to stabilize and deliver mRNAs encoding an engineered ubiquitin ligase to cells. The mRNA nanoplexes enabled proteome editing both in vitro and in mice.

ACS Cent. Sci. 5, 852 (2019).

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