Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
2005-8-19
pubmed:abstractText
The 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5401-13
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15940266-Blotting, Western, pubmed-meshheading:15940266-Cell Nucleus, pubmed-meshheading:15940266-Fluorescent Antibody Technique, pubmed-meshheading:15940266-HeLa Cells, pubmed-meshheading:15940266-Humans, pubmed-meshheading:15940266-Immunoprecipitation, pubmed-meshheading:15940266-Intranuclear Inclusion Bodies, pubmed-meshheading:15940266-Leukemia, Promyelocytic, Acute, pubmed-meshheading:15940266-Microscopy, Confocal, pubmed-meshheading:15940266-Mutagenesis, Site-Directed, pubmed-meshheading:15940266-Neoplasm Proteins, pubmed-meshheading:15940266-Nuclear Proteins, pubmed-meshheading:15940266-Protein Isoforms, pubmed-meshheading:15940266-RNA, Small Interfering, pubmed-meshheading:15940266-SUMO-1 Protein, pubmed-meshheading:15940266-Small Ubiquitin-Related Modifier Proteins, pubmed-meshheading:15940266-Transcription Factors, pubmed-meshheading:15940266-Tumor Suppressor Proteins
pubmed:year
2005
pubmed:articleTitle
Stabilization of PML nuclear localization by conjugation and oligomerization of SUMO-3.
pubmed:affiliation
School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural