The core promoter of human thioredoxin reductase 1

The selenoprotein thioredoxin reductase 1 (TrxR1) carries many vital antiox idant and redox regulatory functions, Its mRNA levels are known to be post- transcriptionally modulated via AUUUA motifs (AU-rich elements (AREs)), but the promoter yet remains unknown. Here we. have cloned and determined the sequence of a 0.8-kilobase pair human genomic. fragment containing the prox imal promoter for TrxR1, which has transcriptional. activity in several dif ferent cell types. The core promoter (-115 to +167) had an increased GC con tent and lacked TATA or CCAAT boxes. It contained a POU motif binding the O ct-1 transcription factor and two sites binding Sp1 and Sp3, which were ide ntified with electrophoretic mobility shift assays using crude nuclear extr acts of A549 cells. The TrxR1 promoter fulfills the typical criteria of a h ousekeeping gene. To our knowledge this is the first housekeeping-type prom oter characterized for a gene with post-transcriptional regulation via ARE motifs generally possessed by transiently expressed proto-oncogenes, nuclea r transcription factors, or cytokines and influencing mRNA stability in res ponse to diverse exogenous factors. Expression of TrxR1 as an ARE-regulated housekeeping gene agrees with a role for the enzyme to maintain a balance between intracellular signaling via reactive oxygen species and protection of cells from excessive oxidative damage.