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B1 oligomerization regulates PML nuclear body biogenesis and leukemogenesis

Author

Listed:
  • Yuwen Li

    (Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine)

  • Xiaodan Ma

    (Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine)

  • Zhiming Chen

    (Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine)

  • Haiyan Wu

    (Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine)

  • Pengran Wang

    (Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine)

  • Wenyu Wu

    (Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine)

  • Nuo Cheng

    (Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine)

  • Longhui Zeng

    (Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine)

  • Hao Zhang

    (Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine)

  • Xun Cai

    (Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine)

  • Sai-Juan Chen

    (Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine)

  • Zhu Chen

    (Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine)

  • Guoyu Meng

    (Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine)

Abstract

ProMyelocyticLeukemia (PML) protein can polymerize into a mega-Dalton nuclear assembly of 0.1–2 μm in diameter. The mechanism of PML nuclear body biogenesis remains elusive. Here, PMLRBCC is successfully purified. The gel filtration and ultracentrifugation analysis suggest a previously unrecognized sequential oligomerization mechanism via PML monomer, dimer, tetramer and N-mer. Consistently, PML B1-box structure (2.0 Å) and SAXS characterization reveal an unexpected networking by W157-, F158- and SD1-interfaces. Structure-based perturbations in these B1 interfaces not only impair oligomerization in vitro but also abolish PML sumoylation and nuclear body biogenesis in HeLaPml-/- cell. More importantly, as demonstrated by in vivo study using transgenic mice, PML-RARα (PR) F158E precludes leukemogenesis. In addition, single cell RNA sequencing analysis shows that B1 oligomerization is an important regulator in PML-RARα-driven transactivation. Altogether, these results not only define a previously unrecognized B1-box oligomerization in PML, but also highlight oligomerization as an important factor in carcinogenesis.

Suggested Citation

  • Yuwen Li & Xiaodan Ma & Zhiming Chen & Haiyan Wu & Pengran Wang & Wenyu Wu & Nuo Cheng & Longhui Zeng & Hao Zhang & Xun Cai & Sai-Juan Chen & Zhu Chen & Guoyu Meng, 2019. "B1 oligomerization regulates PML nuclear body biogenesis and leukemogenesis," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11746-0
    DOI: 10.1038/s41467-019-11746-0
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    Cited by:

    1. Yuemin Ma & Lei Ding & Zhenhai Li & Chun Zhou, 2023. "Structural basis for TRIM72 oligomerization during membrane damage repair," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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