The ubiquitin C-terminal hydrolase UCH-L1 regulates  B-cell proliferation and integrin activation.
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.
Rolén
Ulrika
U
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Freda
Elio
E
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.|Current address: Department of Pediatrics, University of Rome, Tor Vergata, Rome, Italy.
Xie
Jianjun
J
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.|Current address: Hematology Branch, Heart Lung and Blood Institute, Hatfield Clinical Research Center, NIH, Bethesda, MD, USA.
Pfirrmann
Thorsten
T
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.|Current address: Wenner-Grens Institute for Cell Biology, Stockholm University, Stockholm, Sweden.
Frisan
Teresa
T
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Masucci
Maria G
MG
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
D001402:B-Lymphocytes / Q000166:cytology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000502:physiology*; D015854:Up-Regulation
D017931:DNA Primers; D016023:Integrins; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase