AML-1/ETO fusion protein is a dominant negative inhibitor of transcriptional repression by the promyelocytic leukemia zinc finger protein.

摘要: The AML-1/ETO fusion protein, created by the (8;21) translocation in M2-type acute myelogenous leukemia (AML), is a dominant repressive form of AML-1. This effect due to ability ETO portion protein recruit co-repressors promoters AML-1 target genes. t(11;17)(q21;q23)-associated promyelocytic creates zinc finger PLZFt/RARα and, similar manner, inhibits RARα gene expression and myeloid differentiation. PLZF expressed hematopoietic progenitors functions as growth suppressor repressing cyclin A2 other targets. corepressor for potentiates transcriptional repression linking histone deacetylase-containing complex. In transiently transfected cells cell line derived from patient with t(8;21) leukemia, formed tight transient assays, blocked PLZF, even at substoichiometric levels relative PLZF. was dependent on presence domain, which recruits corepressors, could not be rescued overexpression that normally enhance repression. also excluded nuclear matrix reduced its bind cognate DNA-binding site. Finally, interacted PLZF/RARα enhanced repress through RARE. These data show link pathways M2 M3 leukemia.