Cloning and characterization of human polyamine-modulated factor-1, a transcriptional cofactor that regulates the transcription of the spermidine/spermine N-1-acetyltransferase gene

The increased transcription and ultimate superinduction of the spermidine/s permine N-1-acetyltransferase (SSAT) gene has been associated with the anti neoplastic activity of several new antitumor polyamine analogues. In sensit ive tumor cell types, the transcriptional induction appears to be regulated by the constitutive association of the transcription factor Nrf-2 with the recently discovered polyamine-responsive element. Using the yeast two-hybr id system, a new transcriptional cofactor, polyamine-modulated factor-1 (PM F-1), has been identified as a partner protein of Nrf-2 that, in combinatio n with Nrf-2, regulates the polyamine analogue-induced transcription of SSA T, The human PMF-1 gene, located on chromosome 1 near the 1q12/1q21 border, yields an mRNA transcript of similar to 1.2 kilobases that codes for a 165 -amino acid protein with a predicted molecular mass of similar to 20 kDa, T he PMF-1 mRNA appears to increase in response to analogue exposure only in analogue-responsive cells, In addition to the transcriptional regulation of SSAT, PMF-1 or similar factors should be considered in the regulation of o ther polyamine-dependent genes.