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Zfyve16 regulates the proliferation of B-lymphoid cells

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Abstract

Zfyve16 (a.k.a. endofin or endosome-associated FYVE-domain protein), a member of the FYVE-domain protein family, is involved in endosomal trafficking and in TGF-β, BMP, and EGFR signaling. The FYVE protein SARA regulates the TGF-β signaling pathway by recruiting Smad2/3 and accelerating their phosphorylation, thereby altering their susceptibility to TGF-β-mediated T cell suppression. Zfyve16 binds to Smad4 and their binding affects the formation of Smad2/3-Smad4 complex in TGF-β signaling. However, the in vivo function of Zfyve16 remains unknown. In this study, we generated a Zfyve16 knockout mouse strain (Zfyve16KO) and examined its hematopoietic phenotypes and hematopoietic reconstruction ability. The proportion of Tcells in the peripheral blood of Zfyve16KO mice increases compared with that in wild-type mice. This finding is consistent with the role of Zfyve16 in facilitating TGF-β signaling. Unpredictably, B cell proliferation is inhibited in Zfyve16KO mice. The proliferation potential of Zfyve16KO B-lymphoid cells also significantly decreases in vitro. These results suggest that Zfyve16 inhibits the proliferation of T cells, possibly through the TGF-β signaling, but upregulates the proliferation of B-lymphoid cells.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (No. 2016YFC0902800), National Natural Science Foundation of China (Nos. 81230055 and 81530006 to Ruibao Ren), and the Samuel Waxman Cancer Research Foudation Co-PI Program. We thank Huanbin Zhao, Min Wu, Chun Zhang, Mingzhu Liu, Zhangsen Huang, and Lingyun Tang for technical assistance.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Collaborative Innovation Center of Hematology, Collaborative Innovation Center of System Biology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Xuemei Zhao, Donghe Li, Qingsong Qiu, Bo Jiao, Ruihong Zhang, Ping Liu & Ruibao Ren

  2. Department of Biology, Brandeis University, Waltham, MA, 02454, USA

    Ruibao Ren

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  1. Xuemei Zhao
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  2. Donghe Li
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  3. Qingsong Qiu
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  4. Bo Jiao
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  5. Ruihong Zhang
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  6. Ping Liu
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  7. Ruibao Ren
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Correspondence to Ping Liu or Ruibao Ren.

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Zhao, X., Li, D., Qiu, Q. et al. Zfyve16 regulates the proliferation of B-lymphoid cells. Front. Med. 12, 559–565 (2018). https://doi.org/10.1007/s11684-017-0562-3

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  • DOI: https://doi.org/10.1007/s11684-017-0562-3

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