title: Ubiquitin C-terminal hydrolase-L1 interacts with adhesion complexes and promotes cell migration, survival, and anchorage independent growth.
abstract: Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a deubiquitinating enzyme of unknown function that is highly expressed in neurons and overexpressed in several human cancers. UCH-L1 has been implicated in the regulation of phenotypic properties associated with malignant cell growth but the underlying mechanisms have not been elucidated. By comparing cells expressing catalytically active or inactive versions of UCH-L1, we found that the active enzyme enhances cell adhesion, spreading, and migration; inhibits anoikis; and promotes anchorage independent growth. UCH-L1 accumulates at the motile edge of the cell membrane during the initial phases of adhesion, colocalizes with focal adhesion kinase (FAK), p120-catenin, and vinculin, and enhances the formation of focal adhesions, which correlates with enhanced FAK activation. The involvement of UCH-L1 in the regulation of focal adhesions and adherens junctions is supported by coimmunoprecipitation with key components of these complexes, including FAK, paxillin, p120-catenin, β-catenin, and vinculin. UCH-L1 stabilizes focal adhesion signaling in the absence of adhesion, as assessed by reduced caspase-dependent cleavage of FAK following cell detachment and sustained activity of the AKT signaling pathway. These findings offer new insights on the molecular interactions through which the deubiquitinating enzyme regulates the survival, proliferation, and metastatic potential of malignant cells.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden, Box 285, S-171 77 Stockholm, Sweden.
authors.forename: Teresa
authors.initials: T
authors.lastname: Frisan
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Coppotelli
authors.forename: Rikard
authors.initials: R
authors.lastname: Dryselius
authors.forename: Maria G
authors.initials: MG
authors.lastname: Masucci
mesh_terms: D023102:Anoikis; D055162:Biocatalysis; D015153:Blotting, Western; D051177:Catenins / Q000378:metabolism; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions; D006367:HeLa Cells; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D011485:Protein Binding; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D016596:Vinculin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D000095002:Delta Catenin; D000097573:Red Fluorescent Protein
chemical_list: D051177:Catenins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D008164:Luminescent Proteins; D025801:Ubiquitin; D043222:Ubiquitin Thiolesterase; D016596:Vinculin; D051176:beta Catenin; D000095002:Delta Catenin; D000097573:Red Fluorescent Protein; C482860:UCHL1 protein, human; C000722347:CTNND1 protein, human