TY - JOUR
T1 - Targeted protein degradation tools
T2 - Overview and future perspectives
AU - Prozzillo, Yuri
AU - Fattorini, Gaia
AU - Santopietro, Maria Virginia
AU - Suglia, Luigi
AU - Ruggiero, Alessandra
AU - Ferreri, Diego
AU - Messina, Giovanni
N1 - Funding Information:
Funding: This research was funded by the Pasteur Institute of Italy, Fondazione Cenci-Bolognetti (G.M.).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/12
Y1 - 2020/12
N2 - Targeted protein inactivation (TPI) is an elegant approach to investigate protein function and its role in the cellular landscape, overcoming limitations of genetic perturbation strategies. These systems act in a reversible manner and reduce off-target effects exceeding the limitations of CRISPR/Cas9 and RNA interference, respectively. Several TPI have been developed and wisely improved, including compartment delocalization tools and protein degradation systems. However, unlike chemical tools such as PROTACs (PROteolysis TArgeting Chimeras), which work in a wild-type genomic background, TPI technologies require adding an aminoacidic signal sequence (tag) to the protein of interest (POI). On the other hand, the design and optimization of PROTACs are very laborious and time-consuming. In this review, we focus on anchor-away, deGradFP, auxin-inducible degron (AID) and dTAG technologies and discuss their recent applications and advances. Finally, we propose nano-grad, a novel nanobody-based protein degradation tool, which specifically proteolyzes endogenous tag-free target protein.
AB - Targeted protein inactivation (TPI) is an elegant approach to investigate protein function and its role in the cellular landscape, overcoming limitations of genetic perturbation strategies. These systems act in a reversible manner and reduce off-target effects exceeding the limitations of CRISPR/Cas9 and RNA interference, respectively. Several TPI have been developed and wisely improved, including compartment delocalization tools and protein degradation systems. However, unlike chemical tools such as PROTACs (PROteolysis TArgeting Chimeras), which work in a wild-type genomic background, TPI technologies require adding an aminoacidic signal sequence (tag) to the protein of interest (POI). On the other hand, the design and optimization of PROTACs are very laborious and time-consuming. In this review, we focus on anchor-away, deGradFP, auxin-inducible degron (AID) and dTAG technologies and discuss their recent applications and advances. Finally, we propose nano-grad, a novel nanobody-based protein degradation tool, which specifically proteolyzes endogenous tag-free target protein.
KW - Anchor-away
KW - DeGradFP
KW - Degron
KW - DTAG
KW - FKBP12
KW - Nano-grad
KW - Nanobody
KW - Targeted protein degradation (TPD)
KW - Targeted protein inactivation (TPI)
KW - Von Hippel–Lindau (VHL)
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U2 - 10.3390/biology9120421
DO - 10.3390/biology9120421
M3 - Review article
AN - SCOPUS:85096663235
SN - 2079-7737
VL - 9
SP - 1
EP - 15
JO - Biology
JF - Biology
IS - 12
M1 - 421
ER -