Phase Transition and Remodeling Complex Assembly Are Important for SS18-SSX Oncogenic Activity in Synovial Sarcomas

Overview

Journal Nat Commun

Specialty Biology

Date 2022 May 18

PMID 35585082

Authors

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

Affiliations

Soon will be listed here.

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.

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