Scientific background: |
GLRX3 (Glutaredoxin-3) is a protein that in humans is encoded by the GLRX3 gene. It is also known as Picot(Protein kinase C-interacting cousin of Thioredoxin). Hartz (2009)mapped the GLRX3 gene to chromosome 10q26.3 based on an alignment of the GLRX3 sequence with the genomic sequence (build 36.1), Using cotransfection and immunoprecipitation analysis with Jurkat cells, Witte et al. (2000) showed that PICOT interacted with PKC-theta and, more weakly, with PKC-zeta but not with PKC-alpha. Mutation analysis showed that the thioredoxin homology domain of PICOT was required for the interaction. Transfection of PICOT in Jurkat cells reduced basal JNK activity and significantly reduced PKC-theta-induced JNK activation. PICOT also inhibited the transcription factors AP1 and NF-kappa-B .Jeong et al. (2008)stated that Picot inhibits pressure overload-induced cardiac hypertrophy in rodents, concomitant with increased ventricular function and cardiomyocyte contractility. They showed that Picot colocalized with Mlp, which anchors calcineurin to the Z disc in the sarcomere and is critical for calcineurin-Nfat signaling. The C-terminal half of Picot inhibited cardiac hypertrophy, largely by disrupting the Mlp-calcineurin interaction and thereby negatively regulating calcineurin-Nfat signaling. |
References: |
1. Hartz, P. A.Personal Communication.Baltimore, Md. 4/22/2009.
2. Jeong, D., Kim, J. M., Cha, H., Oh, J. G., Park, J., Yun, S.-H., Ju, E.-S., Jeon, E.-S., Hajjar, R. J., Park, W. J.PICOT attenuates cardiac hypertrophy by disrupting calcineurin-NFAT signaling.Circ. Res. 102: 711-719, 2008.
3. Witte, S., Villalba, M., Bi, K., Liu, Y., Isakov, N., Altman, A.Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-kappa-B pathways by PICOT, a novel protein kinase C-interacting protein with a thioredoxin homology domain.J. Biol. Chem. 275: 1902-1909, 2000. |