Thioredoxin regulates cell cycle via the ERK1/2-cyclin D1 pathway.
Thioredoxin (TRX) is a key component of redox regulation and has been indicated to play an essential role in cell survival and growth. Here, we investigated the molecular mechanism of TRX in the regulation of cell survival and growth by using RNA interference (RNAi) in A549 lung cancer and MCF7 breast cancer cells. TRX knockdown did not significantly increase the basal level of cell death without exposure to stress, but CDDP-induced cell death was enhanced. Meanwhile, TRX knockdown resulted in significant cell-cycle arrest at the G(1) phase. Cyclin D1 expression was reduced by TRX knockdown at the protein and mRNA levels. TRX knockdown caused suppression of activation of the cyclin D1 promoter through elements including AP-1. TRX knockdown also reduced the levels of phosphorylated ERK1/2 and the nuclear translocation of ERK 1/2 induced by EGF. These results suggest that TRX is an important regulator of the cell cycle in the G(1) phase via cyclin D1 transcription and the ERK/AP-1 signaling pathways.
Mochizuki
Michika
M
Department of Biological Responses, Institute for Virus Research, Kyoto, Japan.
Kwon
Yong-Won
YW
Yodoi
Junji
J
Masutani
Hiroshi
H
D001483:Base Sequence; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019938:Cyclin D1 / Q000378:metabolism*; D017931:DNA Primers; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013879:Thioredoxins / Q000235:genetics / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D017931:DNA Primers; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D019938:Cyclin D1; D013879:Thioredoxins; D048049:Extracellular Signal-Regulated MAP Kinases; D002945:Cisplatin