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}
}
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 -