The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Reversible Disruption of mSWI/SNF (BAF) Complexes by the SS18-SSX Oncogenic Fusion in Synovial Sarcoma
Open accessAbstract
Summary Recent exon sequencing studies have revealed that over 19% of human tumors have mutations in subunits of mSWI/SNF (BAF) complexes. To investigate the underlying mechanism we studied human synovial sarcoma (SS), in which transformation results from the translocation of exactly 78 amino acids of SSX to the SS18 subunit of BAF complexes. We demonstrate that the SS18-SSX fusion protein competes for assembly with wildtype SS18, forming an altered complex lacking the tumor suppressor BAF47 (hSNF5). The altered complex binds the Sox2 locus and reverses polycomb-mediated repression, resulting in Sox2 activation. Sox2 is uniformly expressed in SS tumors and is essential for proliferation. Increasing the concentration of wildtype SS18 leads to reassembly of wildtype complexes retargeted away from the Sox2 locus, polycomb-mediated repression of Sox2 and cessation of proliferation. This mechanism of transformation depends on only two amino acids of SSX providing a potential foundation for therapeutic intervention.
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Cited by
Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas
Abeshouse, A., Adebamowo, C., Adebamowo, S. N., Akbani, R., Akeredolu, T., Ally, A., Anderson, M. L., Anur, P., Appelbaum, E. L., Armenia, J., et al. (2017) · Cell · doi:10.1016/j.cell.2017.10.014 · Cited by 1,069
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Self-citationCancer-Specific Retargeting of BAF Complexes by a Prion-like Domain
Boulay, G., Sandoval, G. J., Riggi, N., Iyer, S., Buisson, R., Naigles, B., Awad, M. E., Rengarajan, S., Volorio, A., McBride, M. J., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.036 · Cited by 470
Self-citationMichel, B. C., D’Avino, A. R., Cassel, S. H., Mashtalir, N., McKenzie, Z. M., McBride, M. J., Valencia, A. M., Zhou, Q., Bocker, M., Soares, L. M. M., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0221-1 · Cited by 422
Self-citationThe Many Roles of BAF (mSWI/SNF) and PBAF Complexes in Cancer
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Metadata
- Authors
- Kadoch, C., & Crabtree, G. R.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 153
- Issue
- 1
- Pages
- 71-85
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2163261207
- Cited by
- 484
- References
- 40
- FWCI
- 14.25
- Type
- journal article
- Language
- en
- Open access
- bronze
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