Cathepsin X Cleaves Profilin 1 C-Terminal Tyr139 and Influences Clathrin-Mediated Endocytosis

PloS One
Urša Pečar Fonović, Janko Kos

Abstract

Cathepsin X, a cysteine carboxypeptidase, is upregulated in several types of cancer. Its molecular target in tumor cells is profilin 1, a known tumor suppressor and regulator of actin cytoskeleton dynamics. Cathepsin X cleaves off the C-terminal Tyr139 of profilin 1, affecting binding of poly-L-proline ligands and, consequently, tumor cell migration and invasion. Profilin 1 with mutations at the C-terminus, transiently expressed in prostate cancer cells PC-3, showed that Tyr139 is important for proper function of profilin 1 as a tumor suppressor. Cleaving off Tyr139 prevents the binding of clathrin, a poly-L-proline ligand involved in endocytosis. More profilin 1-clathrin complexes were present in PC-3 cells when cathepsin X was inhibited by its specific inhibitor AMS36 or silenced by siRNA. As a consequence, the endocytosis of FITC-labeled dextran and transferrin conjugate was significantly increased. These results constitute the first report of the regulation of clathrin-mediated endocytosis in tumor cells through proteolytic processing of profilin 1.

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Citations

Jun 20, 2019·Cell Cycle·Surinder M SoondAndrey A Zamyatnin
Jul 15, 2020·Biophysics Reviews·Rhonda J Davey, Pierre Dj Moens
Sep 15, 2017·Scientific Reports·Urša Pečar FonovićJanko Kos
Sep 27, 2019·Frontiers in Immunology·Tanja JakošJanko Kos
Jul 22, 2018·Biophysics Reviews·Joelle V F CoumansPierre D J Moens
Apr 25, 2020·Cells·Valeria De PasqualeLuigi Michele Pavone
Feb 6, 2020·ACS Chemical Biology·Simon J MountfordLaura E Edgington-Mitchell
Mar 9, 2021·Current Opinion in Cell Biology·Jonathan Stahl-MeyerMarja Jäättelä

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Methods Mentioned

BETA
transfection
Protein Assay
fluorescence microscopy
confocal microscopy
transfect
proximity ligation
proximity
flow cytometry
ELISA

Software Mentioned

Cell Quest
ZEN
FlowJo

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