Effects of arsenic on the topology and solubility of promyelocytic leukemia (PML)-nuclear bodies.

Abstract

Promyelocytic leukemia (PML) proteins are involved in the pathogenesis of acute promyelocytic leukemia (APL). Trivalent arsenic (As3+) is known to cure APL by binding to cysteine residues of PML and enhance the degradation of PML-retinoic acid receptor α (RARα), a t(15;17) gene translocation product in APL cells, and restore PML-nuclear bodies (NBs). The size, number, and shape of PML-NBs vary among cell types and during cell division. However, topological changes of PML-NBs in As3+-exposed cells have not been well-documented. We report that As3+-induced solubility shift underlies rapid SUMOylation of PML and late agglomeration of PML-NBs. Most PML-NBs were toroidal and granular dot-like in GFPPML-transduced CHO-K1 and HEK293 cells, respectively. Exposure to As3+ and antimony (Sb3+) greatly reduced the solubility of PML and enhanced SUMOylation within 2 h in the absence of changes in the number and size of PML-NBs. However, the prolonged exposure to As3+ and Sb3+ resulted in agglomeration of PML-NBs. Exposure to bismuth (Bi3+), another Group 15 element, did not induce any of these changes. ML792, a SUMO activation inhibitor, reduced the number of PML-NBs and increased the size of the NBs, but had little effect on the As3+-induced solubility change of PML. These results warrant the importance of As3+- or Sb3+-induced solubility shift of PML for the regulation intranuclear dynamics of PML-NBs.

• Authors: Seishiro Hirano, Osamu Udagawa
• Journal: PloS one (PLoS One) Vol. 17 Issue 5 Pg. e0268835 ( 2022) ISSN: 1932-6203 [Electronic] United States
• PMID: 35594310 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Promyelocytic Leukemia Protein
• Transcription Factors
• Arsenic

Topics

• Arsenic (metabolism, pharmacology)
• Cell Nucleus (metabolism)
• HEK293 Cells
• Humans
• Leukemia, Promyelocytic, Acute (metabolism)
• Nuclear Bodies (chemistry)
• Promyelocytic Leukemia Protein (genetics, metabolism)
• Solubility
• Transcription Factors (metabolism)