An ATF/CREB-binding site is essential for cell-specific and inducible transcription of the murine MIP-1β cytokine gene

Abstract The murine macrophage inflammatory protein 1β mRNA ( MIP-1β ) is rapidly and transiently induced in macrophages by lipopolysacharride (LPS), serum or cycloheximide. Functional studies of the MIP-1β proximal promoter indicate that it is cell-specific, and serum- and LPS-responsive in macrophages. A 76-bp proximal promoter sequence (−51 to −127 bp) confers cell-specific and LPS-inducible activity when placed upstream from a heterologous promoter in both orientations. One essential cis -regulatory element within the enhancer-like sequence is an activating transcription factor/cAMP response element (CRE)-binding protein (ATF/CREB)-binding site, although the promoter is not cAMP responsive. Electrophoretic mobility shift assays and mutational analyses suggest that the promoter site is bound by nuclear protein complexes containing cAMP-independent members of the ATF/CREB family of proteins and c-Jun, and are functionally distinct from the AP1-related TPA-response element ( TRE ) binding activity.