Article: Stabilization of PML nuclear localization by conjugation and oligomerization of SUMO-3

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TitleStabilization of PML nuclear localization by conjugation and oligomerization of SUMO-3
AuthorsFu, C1 3
Ahmed, K3
Ding, H3
Ding, X1
Lan, J2
Yang, Z4
Miao, Y3
Zhu, Y2
Shi, Y3
Zhu, J3
Huang, H2
Yao, X1 3
Issue Date2005
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
CitationOncogene, 2005, v. 24 n. 35, p. 5401-5413 [How to Cite?]
DOI: http://dx.doi.org/10.1038/sj.onc.1208714
AbstractThe PML gene of acute promyelocytic leukemia (APL) encodes a cell-growth and tumor suppressor. PML localizes to discrete nuclear bodies (NBs) that are disrupted in APL cells, resulting from a reciprocal chromosome translocation t (15;17). Here we show that the nuclear localization of PML is also regulated by SUMO-3, one of the three recently identified SUMO isoforms in human cells. SUMO-3 bears similar subcellular distribution to those of SUMO-1 and -2 in the interphase nuclear body, which is colocalized with PML protein. However, both SUMO-2 and -3 are also localized to nucleoli, a region lacking SUMO-1. Immunoprecipitated PML protein bears SUMO-3 moiety in a covalently modified form, supporting the notion that PML is conjugated by SUMO-3. To determine the functional relevance of SUMO-3 conjugation on PML molecular dynamics, we suppressed SUMO-3 protein expression using a siRNA-mediated approach. Depletion of SUMO-3 markedly reduced the number of PML-containing NBa and their integrity, which is rescued by exogenous expression of SUMO-3 but not SUMO-1 or SUMO-2. The specific requirement of SUMO-3 for PML nuclear localization is validated by expression of SUMO-3 conjugation defective mutant. Moreover, we demonstrate that oligomerization of SUMO-3 is required for PML retention in the nucleus. Taken together, our studies provide first line of evidence showing that SUMO-3 is essential for PML localization and offer novel insight into the pathobiochemistry of APL. © 2005 Nature Publishing Group All rights reserved.
ISSN0950-9232
2011 Impact Factor: 6.373
2011 SCImago Journal Rankings: 1.216
DOIhttp://dx.doi.org/10.1038/sj.onc.1208714
ISI Accession Number IDWOS:000231222300001
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorFu, C
dc.contributor.authorAhmed, K
dc.contributor.authorDing, H
dc.contributor.authorDing, X
dc.contributor.authorLan, J
dc.contributor.authorYang, Z
dc.contributor.authorMiao, Y
dc.contributor.authorZhu, Y
dc.contributor.authorShi, Y
dc.contributor.authorZhu, J
dc.contributor.authorHuang, H
dc.contributor.authorYao, X
dc.date.accessioned2011-07-29T02:12:10Z
dc.date.available2011-07-29T02:12:10Z
dc.date.issued2005
dc.description.abstractThe PML gene of acute promyelocytic leukemia (APL) encodes a cell-growth and tumor suppressor. PML localizes to discrete nuclear bodies (NBs) that are disrupted in APL cells, resulting from a reciprocal chromosome translocation t (15;17). Here we show that the nuclear localization of PML is also regulated by SUMO-3, one of the three recently identified SUMO isoforms in human cells. SUMO-3 bears similar subcellular distribution to those of SUMO-1 and -2 in the interphase nuclear body, which is colocalized with PML protein. However, both SUMO-2 and -3 are also localized to nucleoli, a region lacking SUMO-1. Immunoprecipitated PML protein bears SUMO-3 moiety in a covalently modified form, supporting the notion that PML is conjugated by SUMO-3. To determine the functional relevance of SUMO-3 conjugation on PML molecular dynamics, we suppressed SUMO-3 protein expression using a siRNA-mediated approach. Depletion of SUMO-3 markedly reduced the number of PML-containing NBa and their integrity, which is rescued by exogenous expression of SUMO-3 but not SUMO-1 or SUMO-2. The specific requirement of SUMO-3 for PML nuclear localization is validated by expression of SUMO-3 conjugation defective mutant. Moreover, we demonstrate that oligomerization of SUMO-3 is required for PML retention in the nucleus. Taken together, our studies provide first line of evidence showing that SUMO-3 is essential for PML localization and offer novel insight into the pathobiochemistry of APL. © 2005 Nature Publishing Group All rights reserved.
dc.description.naturelink_to_subscribed_fulltext
dc.identifier.citationOncogene, 2005, v. 24 n. 35, p. 5401-5413 [How to Cite?]
DOI: http://dx.doi.org/10.1038/sj.onc.1208714
dc.identifier.citeulike221071
dc.identifier.doihttp://dx.doi.org/10.1038/sj.onc.1208714
dc.identifier.eissn1476-5594
dc.identifier.epage5413
dc.identifier.isiWOS:000231222300001
dc.identifier.issn0950-9232
2011 Impact Factor: 6.373
2011 SCImago Journal Rankings: 1.216
dc.identifier.issue35
dc.identifier.pmid15940266
dc.identifier.scopuseid_2-s2.0-24644522876
dc.identifier.spage5401
dc.identifier.urihttp://hdl.handle.net/10722/136783
dc.identifier.volume24
dc.languageeng
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
dc.publisher.placeUnited Kingdom
dc.relation.ispartofOncogene
dc.relation.referencesReferences in Scopus
dc.subject.meshBlotting, Western
dc.subject.meshCell Nucleus - metabolism
dc.subject.meshFluorescent Antibody Technique
dc.subject.meshHeLa Cells
dc.subject.meshHumans
dc.subject.meshImmunoprecipitation
dc.subject.meshIntranuclear Inclusion Bodies - chemistry - metabolism
dc.subject.meshLeukemia, Promyelocytic, Acute - metabolism
dc.subject.meshMicroscopy, Confocal
dc.subject.meshMutagenesis, Site-Directed
dc.subject.meshNeoplasm Proteins - chemistry - metabolism
dc.subject.meshNuclear Proteins - chemistry - metabolism
dc.subject.meshProtein Isoforms - chemistry - metabolism
dc.subject.meshRNA, Small Interfering
dc.subject.meshSUMO-1 Protein - chemistry - metabolism
dc.subject.meshSmall Ubiquitin-Related Modifier Proteins - chemistry - metabolism
dc.subject.meshTranscription Factors - chemistry - metabolism
dc.subject.meshTumor Suppressor Proteins - chemistry - metabolism
dc.titleStabilization of PML nuclear localization by conjugation and oligomerization of SUMO-3
dc.typeArticle
Author Affiliations
  1. Morehouse School of Medicine
  2. Zhejiang University
  3. University of Science and Technology of China
  4. Proteomics Research Laboratory