B1 oligomerization regulates PML nuclear body biogenesis and leukemogenesis

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 and Guoyu Meng ()
Additional contact information
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

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-11746-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11746-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-11746-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().