DIFFERENTIAL INTERACTION OF NUCLEAR FACTORS WITH THE LEUKOCYTE-SPECIFIC PP52 PROMOTER IN B-CELL AND T-CELL

The leukocyte-specific, cytoskeleton-binding pp52 (LSP-1, WP-34) prote in is widely expressed in multiple leukocyte lineages, including B and T lymphocytes, granulocytes, and macrophages. We previously detected a tissue specific promoter preceding the exon encoding the N terminus of the pp52 leukocyte protein, Here we describe the functional charact erization of this promoter and identification of the factors in B and T cells that regulate its activity, The pp52 promoter contains an init iator specifying the unique 5' terminus of pp52 mRNA, tandem pairs of Ets and SP1 motifs, and a lone C/EBP motif, All these motifs are essen tial and collectively control transcriptional activity, DNA binding st udies and Ab supershift assays revealed that different combinations of factors interact with these motifs in B tells vs T cells, The Ets mot ifs are preferentially bound by PU-1 in B cell extracts from all stage s of development, whereas a different Ets family member reacts with th ese motifs in T cell extracts, The C/EBP motif is bound by Ig/EBP-1 in pre-B cell and T cell extracts, but is replaced by nuclear factor-IL- 6 beta or a nuclear factor-IL-6 beta-Ig/EBP-1 heterodimer in plasmacyt oma cell extracts, Despite its reported role as a negative regulator o f transcription, Ig/EBP-1 appears to exert a stimulatory effect on thi s promoter, These findings reveal the Features controlling the pp52 pr omoter in B and T cells and provide the foundation for determining the regulation of this promoter in other leukocyte lineages.