Runx1/AML1 in leukemia: disrupted association with diverse protein partners.
Runx1/AML1, a chromosome 21q22 hematopoietic regulator, is frequently translocated in leukemia. Its protein product, a relatively weak transcriptional activator, becomes an effective transcriptional enhancer or repressor, when co-operating with transcriptional co-activators or co-repressors. Runx1/AML1 association with its partners is disrupted in leukemia. For example, Runx1/AML1 mutations and translocations (e.g. t(8;21), t(12;21) and t(3;21)) impair binding of Runx1/AML1-CBFbeta complexes to Runt motifs in myelopoietically active promoters, preventing normal hematopoiesis. However, Runx1/AML1-associated translocations are not leukemogenic in animal models, suggesting the involvement of yet unidentified regulatory proteins. New candidates are cholinesterases, inhibition of which increases leukemic risk in a manner potentially associated with Runx1/AML1.
Perry
Chava
C
Department of Biological Chemistry, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Eldor
Amiram
A
Soreq
Hermona
H
D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D006410:Hematopoiesis; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D017354:Point Mutation; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014178:Translocation, Genetic
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D014157:Transcription Factors