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

Author

Listed:
  • Yanli Cheng

    (Nankai University)

  • Zhongtian Shen

    (Nankai University)

  • Yaqi Gao

    (Nankai University)

  • Feilong Chen

    (Nankai University)

  • Huisha Xu

    (Nankai University)

  • Qinling Mo

    (Nankai University)

  • Xinlei Chu

    (Tianjin Medical University Cancer Institute and Hospital)

  • Chang-liang Peng

    (Shandong University)

  • Takese T. McKenzie

    (The University of Texas MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences)

  • Bridgitte E. Palacios

    (The University of Texas MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences)

  • Jian Hu

    (The University of Texas MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences)

  • Hao Zhou

    (Nankai University)

  • Jiafu Long

    (Nankai University
    Nankai International Advanced Research Institute (Shenzhen Futian))

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.

Suggested 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, 2022. "Phase transition and remodeling complex assembly are important for SS18-SSX oncogenic activity in synovial sarcomas," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30447-9
    DOI: 10.1038/s41467-022-30447-9
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    References listed on IDEAS

    as
    1. Chengcheng Wang & Zhouyan Guo & Xiechao Zhan & Fenghua Yang & Mingxuan Wu & Xiaofeng Zhang, 2020. "Structure of the yeast Swi/Snf complex in a nucleosome free state," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    2. Yan Han & Alexis A Reyes & Sara Malik & Yuan He, 2020. "Cryo-EM structure of SWI/SNF complex bound to a nucleosome," Nature, Nature, vol. 579(7799), pages 452-455, March.
    3. Junqi Kuang & Ziwei Zhai & Pengli Li & Ruona Shi & Wenjing Guo & Yuxiang Yao & Jing Guo & Guoqing Zhao & Jiangpin He & Shuyang Xu & Chuman Wu & Shengyong Yu & Chunhua Zhou & Linlin Wu & Yue Qin & Baom, 2021. "SS18 regulates pluripotent-somatic transition through phase separation," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
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    Cited by:

    1. Swarnendu Tripathi & Hazheen K. Shirnekhi & Scott D. Gorman & Bappaditya Chandra & David W. Baggett & Cheon-Gil Park & Ramiz Somjee & Benjamin Lang & Seyed Mohammad Hadi Hosseini & Brittany J. Pioso &, 2023. "Defining the condensate landscape of fusion oncoproteins," Nature Communications, Nature, vol. 14(1), pages 1-25, December.

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