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- Title
Phase transition and remodeling complex assembly are important for SS18-SSX oncogenic activity in synovial sarcomas.
- Authors
Cheng, Yanli; Shen, Zhongtian; Gao, Yaqi; Chen, Feilong; Xu, Huisha; Mo, Qinling; Chu, Xinlei; Peng, Chang-liang; McKenzie, Takese T.; Palacios, Bridgitte E.; Hu, Jian; Zhou, Hao; Long, Jiafu
- Abstract
Oncoprotein SS18-SSX is a hallmark of synovial sarcomas. However, as a part of the SS18-SSX fusion protein, SS18's function remains unclear. Here, we depict the structures of both human SS18/BRG1 and yeast SNF11/SNF2 subcomplexes. Both subcomplexes assemble into heterodimers that share a similar conformation, suggesting that SNF11 might be a homologue of SS18 in chromatin remodeling complexes. Importantly, our study shows that the self-association of the intrinsically disordered region, QPGY domain, leads to liquid-liquid phase separation (LLPS) of SS18 or SS18-SSX and the subsequent recruitment of BRG1 into phase-separated condensates. Moreover, our results show that the tyrosine residues in the QPGY domain play a decisive role in the LLPS of SS18 or SS18-SSX. Perturbations of either SS18-SSX LLPS or SS18-SSX's binding to BRG1 impair NIH3T3 cell transformation by SS18-SSX. Our data demonstrate that both LLPS and assembling into chromatin remodelers contribute to the oncogenic activity of SS18-SSX in synovial sarcomas. Oncoprotein SS18-SSX is a hallmark of synovial sarcoma. Here the authors report phase separation of SS18-SSX and the binding of SS18-SSX to chromatin remodeling complex are important for the transformation activity of the oncoprotein SS18-SSX.
- Subjects
SYNOVIOMA; PHASE transitions; CHROMATIN-remodeling complexes; CHIMERIC proteins; CELL transformation; PHASE separation; HETERODIMERS
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-30447-9