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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 alpha degradation

Title: Role of promyelocytic leukemia (PML) sumolation in nuclear body formation, 11S proteasome recruitment, and As2O3-induced PML or PML/retinoic acid receptor alpha degradation
Authors: Lallemand-Breitenbach, V
Zhu, J
Puvion, F
Koken, M
Honore, N
Doubeikovsky, A
Duprez, E
Pandolfi, PP
Puvion, E
Freemont, P
De The, H
Item Type: Journal Article
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.
Issue Date: 18-Jun-2001
Date of Acceptance: 8-May-2001
URI: http://hdl.handle.net/10044/1/69627
DOI: https://dx.doi.org/10.1084/jem.193.12.1361
ISSN: 0022-1007
Publisher: Rockefeller University Press
Start Page: 1361
End Page: 1371
Journal / Book Title: Journal of Experimental Medicine
Volume: 193
Issue: 12
Copyright Statement: © 2001 The Rockefeller University Press.
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
leukemia
interferon
ubiquitin
nuclear matrix
arsenic
CREB BINDING-PROTEIN
RAR-ALPHA
DEPENDENT DEGRADATION
PREMATURE SENESCENCE
SUMO-1 MODIFICATION
SP100 PROTEINS
ONCOGENIC RAS
BODIES
LOCALIZATION
DAXX
Adenosine Triphosphatases
Amino Acid Motifs
Animals
Arsenic Trioxide
Arsenicals
CHO Cells
Cell Line
Cell Nucleus
Cells, Cultured
Cricetinae
Endopeptidases
Mice
Models, Biological
Mutation
Neoplasm Proteins
Nuclear Matrix
Nuclear Proteins
Oxides
Promyelocytic Leukemia Protein
Proteasome Endopeptidase Complex
Protein Isoforms
Protein Transport
Receptors, Retinoic Acid
Retinoic Acid Receptor alpha
SUMO-1 Protein
Transcription Factors
Tumor Suppressor Proteins
Ubiquitins
11 Medical and Health Sciences
Publication Status: Published
Online Publication Date: 2001-06-11
Appears in Collections:Department of Medicine
Faculty of Medicine



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