A new family of growth factor‐like peptides ‘Trefoil’ disulphide loop structures as a common feature in breast cancer associated peptide (pS2), pancreatic spasmolytic polypeptide (PSP), and frog skin peptides (spasmolysins)

Abstract

A new family of growth factor-like peptides 'Trefoil' disulphide loop structures as a common feature in breast cancer associated peptide (pS2), pancreatic spasmolytic polypeptide (PSP), and frog skin peptides (spasmolysins) Four peptides present in completely different biological sources have been shown to exhibit a large degree of structural similarity. The peptides include: (i) a 60 amino acid residue breast cancer associated pS2 peptide isolated from human gastric juice and the culture media of the human breast cancer cell line MCF-7; (ii) a 106 amino acid residue pancreatic spasmolytic polypeptide (PSP) isolated from porcine pancreas and pancreatic juice; and (iii) a 49 and 50 amino acid residue peptide predicted from a cDNA isolated from the skin of the frog, Xenopus luevis. These peptides are characterized by having one (pS2 and the frog peptides) or two (PSP) domains of a highly conserved 38-39 amino acid residue consensus sequence not found in any other known peptides or proteins. The domain sequences contain 6 cysteine residues in nearly the same positions and it is suggested that these 6 residues are linked by 3 disulphide bonds to form a characteristic 'trefoil' disulphide loop structure common in all four peptides. From the sources of which the peptides have been isolated and from experiments showing that PSP has a growth factor stimulatory effect on MCF-7 cells, it is further suggested that these peptides may represent members of a new family of growth factors.Amino acid sequence comparison; Domain structure; Disuhide bond; Receptor binding

TRAIL and inhibitors of apoptosis are opposing determinants for NF-κB-dependent, genotoxin-induced apoptosis of cancer cells

“…Speci®c forkhead transcription factors have been implicated in regulating pro-apoptotic gene expression including Fas ligand (Brunet et al, 1999). Trefoil factor is a cytokine known to promote cell survival (Chen et al, 2000;Suemori et al, 1991;Taupin et al, 2000;Thim, 1989), as is cell adherence to the extracellular matrix protein, ®bronec-tin (Sakai et al, 2001;Zhang et al, 1995). The expression of both trefoil factor and ®bronectin was NF-kB dependent and markedly inhibited in response to etoposide.…”

Characterisation of the single copy trefoil peptides intestinal trefoil factor and pS2 and their ability to form covalent dimers

“…3a). The proposed primary structure of the motif, with its three disulphide loops, resembles a 'trefoil', which is highly resistant to proteolytic and acid degradation [2].…”

Loss of Heterozygosity and Promoter Methylation, but not Mutation, May Underlie Loss of TFF1 in Gastric Carcinoma

“…Trefoil peptides are small and stable molecules characterized by a three-loop structure formed by three cysteine disulfide bonds (Thim, 1989). TFFs are ectopically induced in cells of regenerating tissues surrounding areas of damage during wound healing in ulcerative and inflammatory bowel diseases (Wong et al, 1999;Wright et al, 1993).…”