Imperial College London
Portrait Picture

Prof Ed Tate

Faculty of Natural Sciences, Department of Chemistry

GSK Chair in Chemical Biology
 
 
 
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Contact

 

+44 (0)20 7594 3752e.tate Website CV

 
 
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Assistant

 

Ms Agnes Lee +44 (0)20 7594 9852

 
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Location

 

301BMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kryza:2021:10.1038/s41589-021-00783-w,
author = {Kryza, T and Khan, T and Lovell, S and Harrington, BS and Yin, J and Porazinski, S and Pajic, M and Koistinen, H and Rantala, JK and Dreyer, T and Magdolen, V and Reuning, U and He, Y and Tate, EW and Hooper, JD},
doi = {10.1038/s41589-021-00783-w},
journal = {Nature Chemical Biology},
pages = {776--783},
title = {Substrate-biased activity-based probes identify proteases that cleave receptor CDCP1},
url = {http://dx.doi.org/10.1038/s41589-021-00783-w},
volume = {17},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - CUB domain-containing protein 1 (CDCP1) is an oncogenic orphan transmembrane receptor and a promising target for the detection and treatment of cancer. Extracellular proteolysis of CDCP1 by poorly defined mechanisms induces pro-metastatic signaling. We describe a new approach for the rapid identification of proteases responsible for key proteolytic events using a substrate-biased activity-based probe (sbABP) that incorporates a substrate cleavage motif grafted onto a peptidyl diphenyl phosphonate warhead for specific target protease capture, isolation and identification. Using a CDCP1-biased probe, we identify urokinase (uPA) as the master regulator of CDCP1 proteolysis, which acts both by directly cleaving CDCP1 and by activating CDCP1-cleaving plasmin. We show that coexpression of uPA and CDCP1 is strongly predictive of poor disease outcome across multiple cancers and demonstrate that uPA-mediated CDCP1 proteolysis promotes metastasis in disease-relevant preclinical in vivo models. These results highlight CDCP1 cleavage as a potential target to disrupt cancer and establish sbABP technology as a new approach to identify disease-relevant proteases.
AU  - Kryza,T
AU  - Khan,T
AU  - Lovell,S
AU  - Harrington,BS
AU  - Yin,J
AU  - Porazinski,S
AU  - Pajic,M
AU  - Koistinen,H
AU  - Rantala,JK
AU  - Dreyer,T
AU  - Magdolen,V
AU  - Reuning,U
AU  - He,Y
AU  - Tate,EW
AU  - Hooper,JD
DO  - 10.1038/s41589-021-00783-w
EP  - 783
PY  - 2021///
SN  - 1552-4450
SP  - 776
TI  - Substrate-biased activity-based probes identify proteases that cleave receptor CDCP1
T2  - Nature Chemical Biology
UR  - http://dx.doi.org/10.1038/s41589-021-00783-w
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000640430900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41589-021-00783-w
UR  - http://hdl.handle.net/10044/1/91052
VL  - 17
ER  -
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