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.