Screening the human genome with bioinformatical tools enabled us to find a Novel Tumor Cell Apoptosis Factor (Nerofe) which is encoded by a sequence in chromosome 10 (HUM: 10q25.3; AL133482.15; GI: 15617233; region 16945…17199), which encodes an 84 amino-acids protein with a signal peptide sequence at its N-terminus

In the mouse genome the analog sequence was found in chromosome 19. We found that this new cDNA is expressed mainly in the thymus and partially in the colon and the frontal lobes of the brain. We found that Nerofe is the naïve ligand of T1/ST2 which is a selective death receptor for proliferating cancer cells. The predicted secondary structure of the peptide, its size, solubility and compactability imply that the protein is most likely a novel hormone-peptide.

It was shown that Nerofe binding to T1/ST2 receptor initiates both Caspases 8 and Bcl-2 mediated apoptotic pathways. It was found that Nerofe was unable to induce apoptosis in non-proliferating cells. We argued that the selectivity of Nerofe-induced apoptosis is related to the level of T1/ST2 receptor expression, which are overexpressed in several types of the cancer and inflamed cells. We have also shown that Nerofe inhibits angiogenesis by suppressing the expression of the VEGFA, VEGFR1 receptor and enhancing the expression of IL-10 anti-angiogenic interleukin.

Nerofes signal pathway

Reference

[1] Sandler U., Devary O., Braitbard O., Rubinstein A.M., Friedman Z.Y. O, Ohana J., Kass G. and Devary Y., NEROFE™ – a Novel Human Hormone-peptide with Anti-Cancer Activity, J. of Exp. Therapeutics and Oncology (JETO), v.8, p.327-339, 2010