Effects of arsenic on the topology and solubility of promyelocytic leukemia (PML)-nuclear bodies.
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0268835 |
| _version_ | 1818236475380072448 |
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| author | Seishiro Hirano Osamu Udagawa |
| author_facet | Seishiro Hirano Osamu Udagawa |
| author_sort | Seishiro Hirano |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T12:10:27Z |
| format | Article |
| id | doaj.art-ec1dae87b03c43799aa64554bc0567f1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T12:10:27Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ec1dae87b03c43799aa64554bc0567f12022-12-22T00:24:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01175e026883510.1371/journal.pone.0268835Effects of arsenic on the topology and solubility of promyelocytic leukemia (PML)-nuclear bodies.Seishiro HiranoOsamu UdagawaPromyelocytic 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.https://doi.org/10.1371/journal.pone.0268835 |
| spellingShingle | Seishiro Hirano Osamu Udagawa Effects of arsenic on the topology and solubility of promyelocytic leukemia (PML)-nuclear bodies. PLoS ONE |
| title | Effects of arsenic on the topology and solubility of promyelocytic leukemia (PML)-nuclear bodies. |
| title_full | Effects of arsenic on the topology and solubility of promyelocytic leukemia (PML)-nuclear bodies. |
| title_fullStr | Effects of arsenic on the topology and solubility of promyelocytic leukemia (PML)-nuclear bodies. |
| title_full_unstemmed | Effects of arsenic on the topology and solubility of promyelocytic leukemia (PML)-nuclear bodies. |
| title_short | Effects of arsenic on the topology and solubility of promyelocytic leukemia (PML)-nuclear bodies. |
| title_sort | effects of arsenic on the topology and solubility of promyelocytic leukemia pml nuclear bodies |
| url | https://doi.org/10.1371/journal.pone.0268835 |
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