B1 oligomerization regulates PML nuclear body biogenesis and leukemogenesis
Yuwen Li1, Xiaodan Ma1, Zhiming Chen1
1State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
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.
Related Concept Videos
Regulation of Nuclear Protein Sorting
Nuclear Stability
To hold positively charged protons together...
Nuclear Fusion
A helium nucleus has a mass that is 0.7% less than that of four hydrogen nuclei; this lost mass is converted into energy during the fusion. This reaction produces about...
Non-nuclear Inheritance
Nuclear Transmutation
Regulated mRNA Transport


