The synovial sarcoma translocation protein SYT-SSX2 recruits beta-catenin to the nucleus and associates with it in an active complex.
Localization of beta-catenin in the cell is a key determinant in its decision to function as a critical mediator of cell adhesion at the surface or a transcription activator in the nucleus. SYT-SSX2 is the fusion product of the chromosomal translocation, t(X;18)(p11.2;q11.2), which occurs in synovial sarcoma, a soft tissue tumor. SYT-SSX2 is known to associate with chromatin remodeling complexes and is proposed to be involved in controlling gene expression. We report that SYT-SSX2 plays a direct role in beta-catenin regulation. When expressed in mammalian cells, SYT-SSX2-induced beta-catenin recruitment to the nucleus. Interestingly, known target genes of canonical Wnt were not activated as a result of SYT-SSX2 expression, nor was the nuclear localization of beta-catenin due to one of the signaling pathways normally implicated in this event. beta-Catenin accumulation in the nucleus led to the formation of a transcriptionally active nuclear complex that contained SYT-SSX2 and beta-catenin. More importantly, depletion of SYT-SSX2 in primary synovial sarcoma cells resulted in loss of nuclear beta-catenin signal and a significant decrease in its signaling activity. These results unravel a novel pathway in the control of beta-catenin cellular transport and strongly suggest that SYT-SSX2 contributes to tumor development, in part through beta-catenin signaling.
Pretto
D
D
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Barco
R
R
Rivera
J
J
Neel
N
N
Gustavson
M D
MD
Eid
J E
JE
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D046912:Multiprotein Complexes; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D013584:Sarcoma, Synovial / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D046912:Multiprotein Complexes; D015514:Oncogene Proteins, Fusion; C116512:SYT-SSX fusion protein; D051176:beta Catenin; D019938:Cyclin D1; D050881:E1A-Associated p300 Protein