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Arsenic-Induced SUMO-Dependent Recruitment of RNF4 into PML Nuclear Bodies

In acute promyelocytic leukemia (APL), the promyelocytic leukemia (PML) protein is fused to the retinoic acid receptor alpha (RAR). Arsenic is an effective treatment for this disease as it induces SUMO-dependent ubiquitin-mediated proteasomal degradation of the PML-RAR fusion protein. Here we analyz...

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Autores principales: Geoffroy, Marie-Claude, Jaffray, Ellis G., Walker, Katherine J., Hay, Ronald T.
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993750/
https://www.ncbi.nlm.nih.gov/pubmed/20943951
http://dx.doi.org/10.1091/mbc.E10-05-0449
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author Geoffroy, Marie-Claude
Jaffray, Ellis G.
Walker, Katherine J.
Hay, Ronald T.
author_facet Geoffroy, Marie-Claude
Jaffray, Ellis G.
Walker, Katherine J.
Hay, Ronald T.
author_sort Geoffroy, Marie-Claude
collection PubMed
description In acute promyelocytic leukemia (APL), the promyelocytic leukemia (PML) protein is fused to the retinoic acid receptor alpha (RAR). Arsenic is an effective treatment for this disease as it induces SUMO-dependent ubiquitin-mediated proteasomal degradation of the PML-RAR fusion protein. Here we analyze the nuclear trafficking dynamics of PML and its SUMO-dependent ubiquitin E3 ligase, RNF4 in response to arsenic. After administration of arsenic, PML immediately transits into nuclear bodies where it undergoes SUMO modification. This initial recruitment of PML into nuclear bodies is not dependent on RNF4, but RNF4 quickly follows PML into the nuclear bodies where it is responsible for ubiquitylation of SUMO-modified PML and its degradation by the proteasome. While arsenic restricts the mobility of PML, FRAP analysis indicates that RNF4 continues to rapidly shuttle into PML nuclear bodies in a SUMO-dependent manner. Under these conditions FRET studies indicate that RNF4 interacts with SUMO in PML bodies but not directly with PML. These studies indicate that arsenic induces the rapid reorganization of the cell nucleus by SUMO modification of nuclear body-associated PML and uptake of the ubiquitin E3 ligase RNF4 leading to the ubiquitin-mediated degradation of PML.
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spelling pubmed-29937502011-02-16 Arsenic-Induced SUMO-Dependent Recruitment of RNF4 into PML Nuclear Bodies Geoffroy, Marie-Claude Jaffray, Ellis G. Walker, Katherine J. Hay, Ronald T. Mol Biol Cell Articles In acute promyelocytic leukemia (APL), the promyelocytic leukemia (PML) protein is fused to the retinoic acid receptor alpha (RAR). Arsenic is an effective treatment for this disease as it induces SUMO-dependent ubiquitin-mediated proteasomal degradation of the PML-RAR fusion protein. Here we analyze the nuclear trafficking dynamics of PML and its SUMO-dependent ubiquitin E3 ligase, RNF4 in response to arsenic. After administration of arsenic, PML immediately transits into nuclear bodies where it undergoes SUMO modification. This initial recruitment of PML into nuclear bodies is not dependent on RNF4, but RNF4 quickly follows PML into the nuclear bodies where it is responsible for ubiquitylation of SUMO-modified PML and its degradation by the proteasome. While arsenic restricts the mobility of PML, FRAP analysis indicates that RNF4 continues to rapidly shuttle into PML nuclear bodies in a SUMO-dependent manner. Under these conditions FRET studies indicate that RNF4 interacts with SUMO in PML bodies but not directly with PML. These studies indicate that arsenic induces the rapid reorganization of the cell nucleus by SUMO modification of nuclear body-associated PML and uptake of the ubiquitin E3 ligase RNF4 leading to the ubiquitin-mediated degradation of PML. The American Society for Cell Biology 2010-12-01 /pmc/articles/PMC2993750/ /pubmed/20943951 http://dx.doi.org/10.1091/mbc.E10-05-0449 Text en © 2010 by The American Society for Cell Biology This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
spellingShingle Articles
Geoffroy, Marie-Claude
Jaffray, Ellis G.
Walker, Katherine J.
Hay, Ronald T.
Arsenic-Induced SUMO-Dependent Recruitment of RNF4 into PML Nuclear Bodies
title Arsenic-Induced SUMO-Dependent Recruitment of RNF4 into PML Nuclear Bodies
title_full Arsenic-Induced SUMO-Dependent Recruitment of RNF4 into PML Nuclear Bodies
title_fullStr Arsenic-Induced SUMO-Dependent Recruitment of RNF4 into PML Nuclear Bodies
title_full_unstemmed Arsenic-Induced SUMO-Dependent Recruitment of RNF4 into PML Nuclear Bodies
title_short Arsenic-Induced SUMO-Dependent Recruitment of RNF4 into PML Nuclear Bodies
title_sort arsenic-induced sumo-dependent recruitment of rnf4 into pml nuclear bodies
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993750/
https://www.ncbi.nlm.nih.gov/pubmed/20943951
http://dx.doi.org/10.1091/mbc.E10-05-0449
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