An ATF/CREB-binding site is essential for cell-specific and inducible transcription of the murine MIP-1 beta cytokine gene.
The murine macrophage inflammatory protein 1 beta mRNA (MIP-1 beta) is rapidly and transiently induced in macrophages by lipopolysaccharide (LPS), serum or cycloheximide. Functional studies of the MIP-1 beta 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.
ICRF Cancer Medicine Research Unit, St. James's University Hospital, Leeds, UK.
J
J
Proffitt
G
G
Crabtree
M
M
Grove
P
P
Daubersies
B
B
Bailleul
E
E
Wright
M
M
Plumb
D051696:Activating Transcription Factors; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism*; D002460:Cell Line; D054407:Chemokine CCL4; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics*; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D008969:Molecular Sequence Data; D015846:Monokines / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D051696:Activating Transcription Factors; D001798:Blood Proteins; D054407:Chemokine CCL4; D017362:Cyclic AMP Response Element-Binding Protein; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors