Alternative Splicing Involving the Thioredoxin Reductase Module in Mammals: A Glutaredoxin-Containing Thioredoxin Reductase 1

• DOI: 10.1021/bi048478t
• Publication Date: 2004-09-21T04:49:18Z
• Authors: Dan Su; Vadim N. Gladyshev
• Keywords: Glutaredoxin; Ferredoxin-thioredoxin reductase

Thioredoxin reductase 1 (TR1) is a key component in the thioredoxin system, one of major redox systems mammals that links NADPH and thiol-dependent processes. Mammalian TR1 genes are known to be regulated by alternative splicing. In this report, comparative genomic analyses were used identify characterize species-specific common forms mammalian genes. Six human isoforms identified derived from large number transcripts differed their N-terminal sequences. One isoform resulted exons located 30−70 kb upstream previously core promoter was composed basic module fused glutaredoxin (Grx) domain contained an unusual active site CTRC sequence. This form occurred humans, dogs, chimpanzees but inactivated mice rats. The motif enzyme made inactive Grx assays tested. However, when mutated CPYC, present most Grxs, active. addition, presence interfered with activity, distinguishing other proteins TR fusions. data suggest fusion variable sequences pyridine nucleotide thiol/disulfide oxidoreductase pathway specific cellular functions may control spatial temporal expression transcripts. Our also various extensions TRs often expressed testes.