IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30447-9.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30447-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-30447-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    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.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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.
    2. Tao Huang & Dong Liu & Xiaomin Wang & Junqi Kuang & Manqi Wu & Beibei Wang & Zechuan Liang & Yixin Fan & Bo Chen & Zhaoyi Ma & Yu Fu & Wenhui Zhang & Jin Ming & Yue Qin & Chengchen Zhao & Bo Wang & Du, 2024. "Engineering mouse cell fate controller by rational design," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Mingyue Guo & Fengjun Yang & Lijuan Zhu & Leilei Wang & Zhichao Li & Zhenyu Qi & Vasileios Fotopoulos & Jingquan Yu & Jie Zhou, 2024. "Loss of cold tolerance is conferred by absence of the WRKY34 promoter fragment during tomato evolution," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Li Wang & Jiali Yu & Zishuo Yu & Qianmin Wang & Wanjun Li & Yulei Ren & Zhenguo Chen & Shuang He & Yanhui Xu, 2022. "Structure of nucleosome-bound human PBAF complex," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Tao Huang & Dong Liu & Xiaomin Wang & Junqi Kuang & Manqi Wu & Beibei Wang & Zechuan Liang & Yixin Fan & Bo Chen & Zhaoyi Ma & Yu Fu & Wenhui Zhang & Jin Ming & Yue Qin & Chengchen Zhao & Bo Wang & Du, 2024. "Engineering mouse cell fate controller by rational design," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. Fenghua Yang & Tong Bian & Xiechao Zhan & Zhe Chen & Zhihan Xing & Nicolas A. Larsen & Xiaofeng Zhang & Yigong Shi, 2023. "Mechanisms of the RNA helicases DDX42 and DDX46 in human U2 snRNP assembly," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    5. Sofía Muñoz & Andrew Jones & Céline Bouchoux & Tegan Gilmore & Harshil Patel & Frank Uhlmann, 2022. "Functional crosstalk between the cohesin loader and chromatin remodelers," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Zhaowei Yu & Qi Wang & Qichen Zhang & Yawen Tian & Guo Yan & Jidong Zhu & Guangya Zhu & Yong Zhang, 2024. "Decoding the genomic landscape of chromatin-associated biomolecular condensates," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Dhurjhoti Saha & Solomon Hailu & Arjan Hada & Junwoo Lee & Jie Luo & Jeff A. Ranish & Yuan-chi Lin & Kyle Feola & Jim Persinger & Abhinav Jain & Bin Liu & Yue Lu & Payel Sen & Blaine Bartholomew, 2023. "The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. Vladislav N. Nikolov & Dhara Malavia & Takashi Kubota, 2022. "SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    9. Un Seng Chio & Eugene Palovcak & Anton A. A. Smith & Henriette Autzen & Elise N. Muñoz & Zanlin Yu & Feng Wang & David A. Agard & Jean-Paul Armache & Geeta J. Narlikar & Yifan Cheng, 2024. "Functionalized graphene-oxide grids enable high-resolution cryo-EM structures of the SNF2h-nucleosome complex without crosslinking," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    10. Kwangbeom Hyun & Jihye Ahn & Hyoungmin Kim & Jihyun Kim & Yong-In Kim & Hee-Sung Park & Robert G. Roeder & J. Eugene Lee & Jaehoon Kim, 2024. "The BAF complex enhances transcription through interaction with H3K56ac in the histone globular domain," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30447-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.