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Cadherin juxtamembrane region derived peptides inhibit TGF?1 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 TGF? responses in epithelial cells at the gene expression and protein levels. Peptides from regions closer to the membrane appeared more potent inhibitors of TGF? signaling, blocking Smad3 phosphorylation. Thus inhibiting nuclear translocation of phosphorylated Smad complexes and subsequent transcriptional activation of TGF? signal propagating genes. The peptides demonstrated a peptide-specific potential to inhibit other TGF? superfamily members, such as BMP4.

SUBMITTER: Stavropoulos I

PROVIDER: S-EPMC4201599 | biostudies-literature | 2014 May-Jun

REPOSITORIES: biostudies-literature

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Cadherin juxtamembrane region derived peptides inhibit TGFβ1 induced gene expression.

Stavropoulos Ilias I Golla Kalyan K Moran Niamh N Martin Finian F Shields Denis C DC

Bioarchitecture 20140501 3

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 T ...[more]

PMID: 25108297

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