Dyskeratosis congenita is an inherited disease caused by mutations in genes coding for telomeric components. It was previously reported that expression of a dyskerin-derived
peptide, GSE24.2, increases
telomerase activity, regulates gene expression and decreases DNA damage and oxidative stress in
dyskeratosis congenita patient cells. The
biological activity of short
peptides derived from GSE24.2 was tested and one of them, GSE4, that probed to be active, was further characterized in this article. Expression of this eleven
amino acids long
peptide increased
telomerase activity and reduced DNA damage, oxidative stress and cell senescence in dyskerin-mutated cells. GSE4 expression also activated c-myc and TERT promoters and increase of c-myc, TERT and
TERC expression. The level of
biological activity of GSE4 was similar to that obtained by GSE24.2 expression. Incorporation of a dyskerin
nuclear localization signal to GSE24.2 did not change its activity on promoter regulation and DNA damage protection. However, incorporation of a signal that increases the rate of nucleolar localization impaired GSE24.2 activity. Incorporation of the dyskerin
nuclear localization signal to GSE4 did not alter its
biological activity. Mutation of the
Aspartic Acid residue that is conserved in the
pseudouridine synthase domain present in GSE4 did not impair its activity, except for the repression of c-myc promoter activity and the decrease of c-myc, TERT and
TERC gene expression in dyskerin-mutated cells. These results indicated that GSE4 could be of great therapeutic interest for treatment of
dyskeratosis congenita patients.