title: Cadherin juxtamembrane region derived peptides inhibit TGFβ1 induced gene expression.
abstract: Bioactive peptides in the juxtamembrane regions of proteins are involved in many signaling events. The juxtamembrane regions of cadherins were examined for the identification of bioactive regions. Several peptides spanning the cytoplasmic juxtamembrane regions of E- and N-cadherin were synthesized and assessed for the ability to influence TGFβ responses in epithelial cells at the gene expression and protein levels. Peptides from regions closer to the membrane appeared more potent inhibitors of TGFβ signaling, blocking Smad3 phosphorylation. Thus inhibiting nuclear translocation of phosphorylated Smad complexes and subsequent transcriptional activation of TGFβ signal propagating genes. The peptides demonstrated a peptide-specific potential to inhibit other TGFβ superfamily members, such as BMP4.
authors.affiliation: UCD Conway Institute of Biomolecular and Biomedical Research; University College Dublin; Dublin, Ireland; UCD Complex and Adaptive Systems Laboratory; University College Dublin; Dublin, Ireland; School of Medicine and Medical Science; University College Dublin; Dublin, Ireland.
authors.forename: Ilias
authors.initials: I
authors.lastname: Stavropoulos
authors.affiliation: Molecular and Cellular Therapeutics; Royal College of Surgeons in Ireland; Dublin, Ireland.
authors.forename: Kalyan
authors.initials: K
authors.lastname: Golla
authors.affiliation: Molecular and Cellular Therapeutics; Royal College of Surgeons in Ireland; Dublin, Ireland.
authors.forename: Niamh
authors.initials: N
authors.lastname: Moran
authors.affiliation: UCD Conway Institute of Biomolecular and Biomedical Research; University College Dublin; Dublin, Ireland; School of Biomolecular and Biomedical Sciences; University College Dublin; Dublin, Ireland.
authors.forename: Finian
authors.initials: F
authors.lastname: Martin
authors.affiliation: UCD Conway Institute of Biomolecular and Biomedical Research; University College Dublin; Dublin, Ireland; UCD Complex and Adaptive Systems Laboratory; University College Dublin; Dublin, Ireland; School of Medicine and Medical Science; University College Dublin; Dublin, Ireland.
authors.forename: Denis C
authors.initials: DC
authors.lastname: Shields
mesh_terms: D000595:Amino Acid Sequence; D015820:Cadherins / Q000032:analysis / Q000502:physiology*; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000502:physiology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D021382:Protein Sorting Signals / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D015820:Cadherins; D021382:Protein Sorting Signals; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1
keywords: BMP4; E-cadherin; Jagged; N-cadherin; Smad; TGFβ; adherens junctions; palmitic acid; peptide
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