• Open Access

The ubiquitin C-terminal hydrolase UCH-L1 regulates B-cell proliferation and integrin activation

Authors

  • Ulrika Rolén,

    1. Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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  • Elio Freda,

    1. Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
    2. Current address: Department of Pediatrics, University of Rome, Tor Vergata, Rome, Italy
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  • Jianjun Xie,

    1. Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
    2. Current address: Hematology Branch, Heart Lung and Blood Institute, Hatfield Clinical Research Center, NIH, Bethesda, MD, USA
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  • Thorsten Pfirrmann,

    1. Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
    2. Current address: Wenner-Grens Institute for Cell Biology, Stockholm University, Stockholm, Sweden
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  • Teresa Frisan,

    1. Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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  • Maria G. Masucci

    Corresponding author
    1. Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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Correspondence to: Maria G. MASUCCI,
CMB, Karolinska Institutet, Box 285,
S-171 77 Stockholm, Sweden.
Tel.: +46 (0)8 54286755
Fax: +46 8 337412
E-mail: Maria.Masucci@ki.se

Abstract

The ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a deubiquitinating enzyme that catalyses the hydrolysis of polyubiquitin precursors and small ubiquitin adducts. UCH-L1 has been detected in a variety of malignant and metastatic tumours but its biological function in these cells is unknown. We have previously shown that UCH-L1 is highly expressed in Burkitt’s lymphoma (BL) and is up-regulated upon infection of B lymphocytes with Epstein–Barr virus (EBV). Here we show that knockdown of UCH-L1 by RNAi inhibits the proliferation of BL cells in suspension and semisolid agar and activates strong LFA-1-dependent homotypic adhesion. Induction of cell adhesion correlated with cation-induced binding to ICAM-1, clustering of LFA-1 into lipid rafts and constitutive activation of the Rap1 and Rac1 GTPases. Expression of a catalytically active UCH-L1 promoted the proliferation of a UCH-L1-negative EBV transformed lymphoblastoid cell line (LCL) and inhibited cell adhesion, whereas a catalytic mutant had no effect, confirming the requirement of UCH-L1 enzymatic activity for the regulation of these phenotypes. Our results identify UCH-L1 as a new player in the signalling pathways that promote the proliferation and invasive capacity of malignant B cells.

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