Transcriptional Attenuation of PIM-1 Gene

Levels of the mRNA for PIM-1, a protooncogene encoding a cytoplasmic serine threonine kinase show a wide variation among tissues and cell lines, although this gene is transcribed from a GC- rich housekeeping promoter. Previous studies have failed to identify tissue specific elements in the PIM-I promoter raising the possibility that these elements might reside within the gene. Transient transfections of Luciferase reporter gene constructs into the chronic myelogenous leukemia cell line K562 (which expresses high levels of PIM-1 mRNA) demonstrate that the 1.7kbp PIM-I promoter sequences alone were three times more efficient than constructs driven by the promoter + PIM-1 genomic sequences. Nuclear run on assays of nascent RNA from K562 cells revealed premature transcriptional termination within the PIM-l gene. Thus, PIM-1 gene may be constitutively transcribed in all tissues and transcriptional attenuation could be one of the mechanisms regulating the observed differences in steady state levels of mRNA.