The AML1/ETO fusion protein blocks transactivation of the GM-CSF promoter by AML1B.

摘要: The t(8;21) translocation, commonly found in acute myelogenous leukemia (AML), generates a fusion protein containing N-terminal AML1 and C-terminal ETO amino acids. human gene encodes several related proteins that specifically bind to the sequence TGT/cGGT, located promoter regions of variety hematopoietic growth factor genes. To examine abilities AML1B (which contains 479 acids), shorter AML1A isoform acids 1-250), AML1/ETO 1-177) stimulate transcription from GM-CSF promoter, we performed co-transfection experiments T cells using promoter-CAT reporter plasmid expression vectors contain cDNAs for one above proteins. Our data demonstrate AML1B, but not or transactivates requiring TGTGGT contained between base pairs -68 -53. Furthermore, show AML1/ETO, AML1A, inhibits ability CAT expression. Electrophoretic mobility shift assays demonstrated specific binding sequence, which does require sequences immediately upstream this site. support role as transcriptional activator establish can act dominant negative on promoter. Although GM-CSF, it may function by inhibiting normal activity AML with translocation.