Phase transition and remodeling complex assembly are important for SS18-SSX oncogenic activity in synovial sarcomas.

Yanli Cheng, Zhongtian Shen, Yaqi Gao, Feilong Chen, Huisha Xu, Qinling Mo, Xinlei Chu, Chang-Liang Peng, Takese T McKenzie, Bridgitte E Palacios, Jian Hu, Hao Zhou, Jiafu Long

Nature communications 2022 May 18

filter terms:

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. © 2022. The Author(s).

Citation

Yanli Cheng, Zhongtian Shen, Yaqi Gao, Feilong Chen, Huisha Xu, Qinling Mo, Xinlei Chu, Chang-Liang Peng, Takese T McKenzie, Bridgitte E Palacios, Jian Hu, Hao Zhou, Jiafu Long. Phase transition and remodeling complex assembly are important for SS18-SSX oncogenic activity in synovial sarcomas. Nature communications. 2022 May 18;13(1):2724