Proteolytic cleavage of Trop2 at Arg87 is mediated by matriptase and regulated by Val194.

Abstract:

:Proteolytic processing is an important post-translational modification affecting protein activity and stability. In the current study, we investigate the N-terminal cleavage of Trop2, a protein which is overexpressed in many cancers. We demonstrate that Trop2 is cleaved at Arg87 by a transmembrane serine protease, matriptase. Homology modeling and site-directed mutagenesis of amino acids in close proximity to the matriptase cleavage site reveal the importance of Val194 in regulating Trop2 cleavage. Co-immunoprecipitation studies confirm that amino acid substitutions at Arg87, Thr88, Lys189, Val194, and His195 do not affect Trop2 dimerization. However, cleavage of wild-type Trop2 by matriptase is inhibited when it is allowed to dimerize with a V194 A mutant monomer, further confirming the role of Val194 in matriptase-mediated N-terminal cleavage.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Kamble PR,Rane S,Breed AA,Joseph S,Mahale SD,Pathak BR

doi

10.1002/1873-3468.13899

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

3156-3169

issue

19

eissn

0014-5793

issn

1873-3468

journal_volume

594

pub_type

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