B1 oligomerization regulates PML nuclear body biogenesis and leukemogenesis.

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, PML_RBCC 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 HeLa^Pml-/- cell. More importantly, as demonstrated by in vivo study using transgenic mice, PML-RARα (P

SUBMITTER: Li Y 

PROVIDER: S-EPMC6706441 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature