Oxidative stress-induced assembly of PML nuclear bodies controls sumoylation of partner proteins.

The promyelocytic leukemia (PML) protein organizes PML nuclear bodies (NBs), which are stress-responsive domains where many partner proteins accumulate. Here, we clarify the basis for NB formation and identify stress-induced partner sumoylation as the primary NB function. NB nucleation does not rely primarily on intermolecular interactions between the PML SUMO-interacting ...
motif (SIM) and SUMO, but instead results from oxidation-mediated PML multimerization. Oxidized PML spherical meshes recruit UBC9, which enhances PML sumoylation, allow partner recruitment through SIM interactions, and ultimately enhance partner sumoylation. Intermolecular SUMO-SIM interactions then enforce partner sequestration within the NB inner core. Accordingly, oxidative stress enhances NB formation and global sumoylation in vivo. Some NB-associated sumoylated partners also become polyubiquitinated by RNF4, precipitating their proteasomal degradation. As several partners are protein-modifying enzymes, NBs could act as sensors that facilitate and confer oxidative stress sensitivity not only to sumoylation but also to other post-translational modifications, thereby explaining alterations of stress response upon PML or NB loss.
Mesh Terms:
Animals, CHO Cells, COS Cells, Cell Aging, Cell Nucleus, Cercopithecus aethiops, Cricetinae, Cricetulus, HeLa Cells, Humans, Mice, Nuclear Proteins, Oxidative Stress, Protein Transport, Reactive Oxygen Species, Small Ubiquitin-Related Modifier Proteins, Sumoylation, Transcription Factors, Tumor Suppressor Proteins, Ubiquitin-Conjugating Enzymes
J. Cell Biol.
Date: Mar. 17, 2014
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