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Upstream signaling requirements of retinoic acid (RA)-induced blr1 expression and downstream signaling consequences of blr1 over-expression in a human myeloid leukemia cell line demonstrate that mitogen-activated protein kinase (MAPK) signaling complexes are involved in both avenues. RA-induced myeloid differentiation and G₁/G₀ growth arrest of HL-60 cells is known to require the activation of the RARα and RXR retinoid receptors, as well as activation of the MAPK, ERK2. Transcriptional activation of the Burkitt's lymphoma receptor 1 (blr1) gene occurs early during RA-induced differentiation of HL-60 cells and requires these same three activating processes. The use of retinoid ligands that activate either the RARα or the RXR retinoid receptors revealed that blr1 mRNA induction was detectable only when both RARα and RXR were activated. Neither the RARα nor RXR selective ligands alone induced …