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 |
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PML protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/SUMO-1 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/SUMO2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Small Ubiquitin-Related Modifier...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
|
pubmed:status |
MEDLINE
|
pubmed:month |
Aug
|
pubmed:issn |
0950-9232
|
pubmed:author |
pubmed-author:AhmedKashifK,
pubmed-author:FuChuanhaiC,
pubmed-author:HILDWW,
pubmed-author:HuangHeH,
pubmed-author:HushengDingD,
pubmed-author:LanJianpingJ,
pubmed-author:MiaoYongY,
pubmed-author:ShiYunyuY,
pubmed-author:YangZhihongZ,
pubmed-author:YaoXuebiaoX,
pubmed-author:ZhuJingdeJ,
pubmed-author:ZhuYuanyuanY
|
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
|