Linked Life Data

21513699

Source:http://linkedlifedata.com/resource/pubmed/id/21513699

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-5-16
pubmed:abstractText
Methylation of lysine 27 on histone H3 by the polycomb repressive complex 2 (PRC2) leads to transcriptional repression of genes which are critical to development. PRC2 core complex is composed of the histone methyltransferase EZH2, EED, and SUZ12. Knockdown of any of the PRC2 core subunits results in a concomitant loss of the other subunits which is mediated by the ubiquitin (Ub)-proteasome system (UPS). Inhibition of cellular methyltransferases by 3-deazaneplanocin A (DZNep) also leads to dissociation of the PRC2 complex and rapid degradation of its subunits. Interestingly, the expression of several Ub ligases was induced following DZNep treatment, suggesting that PRC2 might repress the Ub ligase(s) that target its subunits for degradation. Here we confirm that individual PRC2 subunits are ubiquitinated and rapidly degraded by the proteasome. One of the DZNep-induced Ub ligases, PRAJA1, can target PRC2 subunits for proteasomal degradation. PRAJA1 directly ubiquitinates individual PRC2 subunits in a cell free system, which leads to their proteasomal degradation. Expression of PRAJA1 but not of an inactive RING finger mutant of the protein, enhanced the degradation of individual PRC2 subunits in cells. Taken together, our results suggest a role for PRAJA1 in regulating the level of PRC2 by targeting its free subunits for Ub-mediated proteasomal degradation.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/3-deazaneplanocin, http://linkedlifedata.com/resource/pubmed/chemical/Adenosine, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/EZH2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/PJA1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex, http://linkedlifedata.com/resource/pubmed/chemical/Protein Methyltransferases, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases, http://linkedlifedata.com/resource/pubmed/chemical/polycomb group proteins
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1090-2104
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
13
pubmed:volume
408
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
393-8
pubmed:dateRevised
2011-8-31
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
PRAJA1 is a ubiquitin ligase for the polycomb repressive complex 2 proteins.
pubmed:affiliation
Center for Vascular and Tumor Biology, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't