The leukemogenic t ( 8 ; 21 ) fusion protein AML 1-ETO controls rRNA genes and associates with nucleolar-organizing regions at mitotic chromosomes

The leukemogenic t(8;21) fusion protein AML1-ETO controls rRNA genes and associates with nucleolar-organizing regions at mitotic chromosomes" (2008). Cell and Developmental Biology Publications and Presentations. Paper 80. Introduction The most frequent target of chromosomal translocations in acute myeloid leukemia (AML) is the Runt-related transcription factor RUNX1/AML1, a key regulator of hematopoiesis (Setoguchi et al. directly regulates multiple distinct myeloid and lymphoid genes that are involved in hematopoietic lineage commitment (Huang et al. The protein contains an N-terminal DNA-binding domain (runt-homology domain) and a C-terminal regulatory domain that contains a nuclear-matrix-targeting signal (NMTS) and several context-dependent transcriptional activation or repression domains (Wheeler et al. Peterson et al., 2007a). AML1-ETO retains the DNA-binding function of the RUNX1/AML1 protein but does not contain the transactivation domain or the nuclear-matrix-targeting signal (NMTS) of RUNX1/AML1 (Zeng et al., 1997; McNeil et al., 1999). Previous studies have shown that exogenously expressed RUNX1/AML1 and AML1-ETO exhibit differential subnuclear targeting, which might be responsible in part for the aberrant function of the fusion protein (McNeil et al., 1999; Barseguian et

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