Expression of a thioredoxin-related protein-1 is induced by prostaglandin E(2).
Prostaglandin E(2) (PGE(2)) plays an important role in protection of the gastric mucosa against various damaging agents and growth-inhibitory activity on tumor cells. However, the precise regulation mechanism of PGE(2) in gastric cancer cells is still unclear. In this study, we isolated a gene, which is regulated by PGE(2) in SNU-1, human gastric adenocarcinoma cells, using differential display RT-PCR (DD RT-PCR) and characterized the function of the gene induced by PGE(2). The full-length cDNA of the gene was cloned by the rapid amplification of cDNA ends method. The 1659 base pair cDNA consists of a 30-nt 5'-noncoding region, an 891-nt open reading frame and a 738-nt 3'noncoding region that includes a poly (A) signal. As a result of protein motif search, we found that it has a conserved thioredoxin-active site, Cys-Gly-Pro-Cys and a Myb-DNA binding domain repeat signature. Thus, we designated this gene product as thioredoxin-related protein-1, TRP-1. TRP-1 was expressed in a lower extent in renal, gastric and colon cancer tissues and is translated into 33 kDa protein in nuclear and cytoplasmic fractions. TRP-1 has a thioredoxin activity, which was detected using the insulin disulfide reduction assay. Another potential role of TRP-1 is repression of B-Myb activity through direct binding to B-Myb, a transcriptional factor induced at G1-S transition. Finally, TRP-1 overexpression inhibits mammalian cell proliferation and specifically predispose to G0/G1 phase arrest. In conclusion, these results imply that TRP-1 is a mammalian thioredoxin and plays as a transcriptional repressor through direct binding to the transcription factor B-Myb.
Kim
Kye Young
KY
Department of Biomedical Sciences, National Institute of Health, Seoul 122-701, Korea.
Lee
June Woo
JW
Park
Min Seon
MS
Jung
Myeong Ho
MH
Jeon
Gyoung A
GA
Nam
Myeong Jin
MJ
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000595:Amino Acid Sequence; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D018076:DNA, Complementary / Q000032:analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D015232:Dinoprostone / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D013879:Thioredoxins / Q000096:biosynthesis*; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; C504766:TXNL1 protein, human; D015534:Trans-Activators; D013879:Thioredoxins; D015232:Dinoprostone