Differential roles of C/EBP beta regulatory domains in specifying MCP-1 and IL-6 transcription.
C/EBPbeta is a member of the CCAAT/enhancer binding protein family of transcription factors and has been shown to be a critical transcriptional regulator of various proinflammatory genes, including IL-6 and MCP-1. To examine the roles of the C/EBPbeta transactivation and regulatory domains in LPS-induced MCP-1 and IL-6 expression, we expressed various N-terminal truncations and deletions of C/EBPbeta in P388 murine B lymphoblasts, which lack endogenous C/EBPbeta expression and are normally unresponsive to LPS for expression of IL-6 and MCP-1. Unexpectedly, a region between amino acids 105 and 212 of C/EBPbeta that includes regulatory domains 1 and 2 facilitates C/EBPbeta activation of IL-6 expression, while having an inhibitory effect on MCP-1 expression. Thus, this region can mediate promoter-specific effects on cytokine and chemokine gene transcription. LIP, the naturally occurring truncated form of C/EBPbeta, largely retains these regulatory domains and stimulates IL-6 but not MCP-1 transcription.
Spooner
Chauncey J
CJ
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Guo
Xiangrong
X
Johnson
Peter F
PF
Schwartz
Richard C
RC
D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000502:physiology*; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D007941:Leukemia P388; D051379:Mice; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D014158:Transcription, Genetic / Q000276:immunology*
D022782:CCAAT-Enhancer-Binding Protein-beta; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D010446:Peptide Fragments