Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-4-25
pubmed:abstractText
The AML1/ETO and PML/RARalpha leukemia fusion proteins induce acute myeloid leukemia by acting as transcriptional repressors. They interact with corepressors, such as N-CoR and SMRT, that recruit a multiprotein complex containing histone deacetylases on crucial myeloid differentiation genes. This leads to gene repression contributing to generate a differentiation block. We expressed in leukemia cells containing PML/RARalpha and AML1/ETO N-CoR protein fragments derived from fusion protein/corepressor interaction surfaces. This blocks N-CoR/SMRT binding by these fusion proteins, and disrupts the repressor protein complex. In consequence, the expression of genes repressed by these fusion proteins increases and differentiation response to vitamin D3 and retinoic acid is restored in previously resistant cells. The alteration of PML/RARalpha-N-CoR/SMRT connections triggers proteasomal degradation of the fusion protein. The N-CoR fragments are biologically effective also when directly transduced by virtue of a protein transduction domain. Our data indicate that fusion protein activity is permanently required to maintain the leukemia phenotype and show the route to developing a novel therapeutic approach for leukemia, based on its molecular pathogenesis.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-10233871, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-10477521, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-10573424, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-10611294, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-10617569, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-10617570, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-10617663, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-10652267, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-10688806, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-10856932, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-10882117, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-10882118, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-10942402, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-11038364, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-11196162, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-11305111, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-11704854, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-11834837, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-12032781, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-12091906, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-12098689, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-12191632, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-12351412, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-12417632, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-12475933, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-12563308, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-12669051, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-12677018, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-1311253, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-1319828, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-1320955, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-14506472, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-14636558, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-14729951, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-14980219, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-15096541, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-15531890, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-1995093, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-7772516, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-8394219, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-8400247, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-8874178, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-8890168, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-9192750, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-9353180, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-9462740, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-9486654, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-9724795, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-9746761, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-9819404, http://linkedlifedata.com/resource/pubmed/commentcorrection/15729358-9819405
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AML1-ETO fusion protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cholecalciferol, http://linkedlifedata.com/resource/pubmed/chemical/Core Binding Factor Alpha 2 Subunit, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/NCOR1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/NCOR2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Co-Repressor 1, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Co-Repressor 2, http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Fusion, http://linkedlifedata.com/resource/pubmed/chemical/Peptides, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin, http://linkedlifedata.com/resource/pubmed/chemical/promyelocytic leukemia-retinoic...
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0261-4189
pubmed:author
pubmed:issnType
Print
pubmed:day
23
More...