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Cited by 488

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Role of Promyelocytic Leukemia (Pml) Sumolation in Nuclear Body Formation, 11s Proteasome Recruitment, and as2O3-Induced Pml or Pml/Retinoic Acid Receptor α Degradation

Open access
Lallemand-Breitenbach, Valérie, Zhu, Jun, Puvion, Francine, Koken, Marcel, Honoré, Nicole, Doubeikovsky, Alexandre, Duprez, Estelle, Pandolfi, Pier Paolo, Puvion, Edmond, Freemont, Paul, de Thé, Hugues·2001·The Journal of Experimental Medicine

Abstract

Promyelocytic leukemia (PML) is the organizer of nuclear matrix domains, PML nuclear bodies (NBs), with a proposed role in apoptosis control. In acute promyelocytic leukemia, PML/retinoic acid receptor (RAR) α expression disrupts NBs, but therapies such as retinoic acid or arsenic trioxide (As2O3) restore them. PML is conjugated by the ubiquitin-related peptide SUMO-1, a process enhanced by As2O3 and proposed to target PML to the nuclear matrix. We demonstrate that As2O3 triggers the proteasome-dependent degradation of PML and PML/RARα and that this process requires a specific sumolation site in PML, K160. PML sumolation is dispensable for its As2O3-induced matrix targeting and formation of primary nuclear aggregates, but is required for the formation of secondary shell-like NBs. Interestingly, only these mature NBs harbor 11S proteasome components, which are further recruited upon As2O3 exposure. Proteasome recruitment by sumolated PML only likely accounts for the failure of PML-K160R to be degraded. Therefore, studying the basis of As2O3-induced PML/RARα degradation we show that PML sumolation directly or indirectly promotes its catabolism, suggesting that mature NBs could be sites of intranuclear proteolysis and opening new insights into NB alterations found in viral infections or transformation.

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Metadata

Authors
Lallemand-Breitenbach, V., Zhu, J., Puvion, F., Koken, M., Honoré, N., Doubeikovsky, A., Duprez, E., Pandolfi, P. P., Puvion, E., Freemont, P., & de Thé, H.
Venue
The Journal of Experimental Medicine
Published
2001-06-11
Volume
193
Issue
12
Pages
1361-1372
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
OpenAlex
W2107954651
Cited by
488
References
2
FWCI
10.21
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Role of Promyelocytic Leukemia (Pml) Sumolation in Nuclear Body Formation, 11s Proteasome Recruitment, and as2O3-Induced Pml or Pml/Retinoic Acid Receptor α Degradation. https://app.cochat.ai/papers/10.1084/jem.193.12.1361
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Lallemand-Breitenbach, V., Zhu, J., Puvion, F., Koken, M., Honoré, N., Doubeikovsky, A., Duprez, E., Pandolfi, P. P., Puvion, E., Freemont, P., & de Thé, H. (2001). Role of Promyelocytic Leukemia (Pml) Sumolation in Nuclear Body Formation, 11s Proteasome Recruitment, and as2O3-Induced Pml or Pml/Retinoic Acid Receptor α Degradation. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.193.12.1361

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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