P-6 - Thioredoxin related protein of 14 kDa (TRP14, TXNDC17) represses Nrf2 and NFκB activities and augments HIF activation

Abstract

Thioredoxin related protein of 14 kDa is a cytosolic protein of the thioredoxin fold family expressed in all tissues and an efficient substrate of the selenoprotein thioredoxin reductase 1. TRP14 cannot support classical Trx1 substrates such as peroxiredoxins, methionine sulfoxide reductases or ribonucleotide reductase, but affects NFκB signaling. However, it is efficient in reducing L-cystine and support S-denitrosylation reactions, reduce protein persulfides or reactivate oxidized protein tyrosine phosphatase PTP1B. These and other observations suggest that TRP14 may have dedicated roles in cellular signaling pathways, which was studied here. Using our previously developed pTRAF, we assessed activation patterns of the transcription factors Nrf2, NFκB and HIF in HEK293 cells with or without modulated TRP14 levels. Our preliminary results suggest that TRP14 is an unusual member of the Trx system, in that TRP14 may act as a repressor of NRF2, modulate HIF activation under hypoxia as well as acting as a weak repressor of NFκB activation. Further analyses are needed to fully evaluate the pTRAF readout also including additional methodologies Our results point towards the role of TRP14 as a dedicated fine-tuning modulator of redox regulated signaling pathways.