AN ATF CREB-BINDING SITE IS ESSENTIAL FOR CELL-SPECIFIC AND INDUCIBLETRANSCRIPTION OF THE MURINE MIP-1-BETA CYTOKINE GENE/

The murine macrophage inflammatory protein IP mRNA (MIP-IB) is rapidly and transiently induced in macrophages by lipopolysacharride (LPS), s erum or cycloheximide. Functional studies of the MIP-1 beta proximal p romoter indicate that it is cell-specific, and serum- and LPS-responsi ve in macrophages. A 76-bp proximal promoter sequence (-51 to - 127 bp ) confers cell-specific and LPS-inducible activity when placed upstrea m 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. Ele ctrophoretic mobility shift assays and mutational analyses suggest tha t the promoter site is bound by nuclear protein complexes containing c AMP-independent members of the ATF/CREB family of proteins and c-Jun, and are functionally distinct from the AP1-related TPA-response elemen t (TRE) binding activity.