Cloning and characterization of the mouse polyamine-modulated factor-1 (mPMF-1) gene: an alternatively spliced homologue of the human transcription factor

The natural polyamines and their analogues have been implicated in transcri ptional regulation of specific genes. Human polyamine-modulated factor-1 (h PMF-1) was the first polyamine-responsive transcription factor identified. Here the mouse homologue of the hPMF-1 gene is described. Interestingly, th e mouse gene (mPMF-1) codes for two alternatively spliced mRNAs. Both of th e mouse splice variants, PMF-1S and mPMF-1L, possess C-terminal coiled-coil domains nearly identical to that found in hPMF-1 and are highly homologous with the human protein. The C-terminal coiled-coil structure is necessary for transcriptional activation. However, the shorter protein, mPMF-1S, does not contain an N-terminal coiled-coil region as do both hPMF-1 and the lon ger mPMF-1L. mPMF-1L mRNA codes for a protein of 202 amino acids, 37 amino acids longer than the human protein. By contrast, mPMF-1S codes for only 13 3 amino acids, as a result of two exons being omitted compared with mPMF-1L . Both mouse transcription factors can interact with Nrf-2 (nuclear factor- E2-related factor 2), the normal partner of hPMF-1, substantiating the impo rtance of the C-terminal coiled-coil region responsible for this interactio n. Finally, the expression of mPMF-1 is induced when mouse M1 myeloid leuka emia cells are exposed to polyamine analogues, suggesting control similar t o that observed for the hPMF-1.