Characterization of the interaction between the transcription factors human polyamine modulated factor (PMF-1) and NF-E2-related factor 2 (Nrf-2) in the transcriptional regulation of the spermidine/spermine N-1-acetyltransferase (SSAT) gene

Polyamines and polyamine analogues have been demonstrated to modulate the t ranscription of various genes. Spermidine/ spermine N-1-acetyltransferase ( SSAT) is transcriptionally regulated through the interaction of at least tw o trans-acting transcription factors, NF-E2-related factor 2 (Nrf-2) and PM F-1 (polyamine modulated factor-1). Nrf-2 has previously been shown to regu late transcription of other genes through interactions between its C-termin al leucine zipper and the leucine-zipper region of other members of the sma ll Maf protein family (the term 'Maf' is derived from musculoaponeurotic-fi brosarcoma virus). Here it is demonstrated that the interaction between Nrf -2 and PMF-1 is mediated through the binding of the leucine-zipper region o f Nrf-2 and a C-terminal coiled-coil region of PMF-1 that does not contain a leucine zipper. Mutations that interrupt either the leucine zipper of Nrf -2 or the coiled-coil region of PMF-1 are demonstrated to alter the ability of these factors to interact, thus their ability to regulate the transcrip tion of the SSAT gene is lost.