title: Antagonistic Effect of a Salivary Proline-Rich Peptide on the Cytosolic Ca2+ Mobilization Induced by Progesterone in Oral Squamous Cancer Cells.
abstract: A salivary proline-rich peptide of 1932 Da showed a dose-dependent antagonistic effect on the cytosolic Ca2+ mobilization induced by progesterone in a tongue squamous carcinoma cell line. Structure-activity studies showed that the activity of the peptide resides in the C-terminal region characterized by a proline stretch flanked by basic residues. Furthermore, lack of activity of the retro-inverso peptide analogue suggested the involvement of stereospecific recognition. Mass spectrometry-based shotgun analysis, combined with Western blotting tests and biochemical data obtained with the Progesterone Receptor Membrane Component 1 (PGRMC1) inhibitor AG205, showed strong evidence that p1932 performs its modulatory action through an interaction with the progesterone receptor PGRMC1, which is predominantly expressed in this cell line and, clearly, plays a role in progesterone induced Ca2+ response. Thus, our results point to p1932 as a modulator of the transduction signal pathway mediated by this protein and, given a well-established involvement of PGRMC1 in tumorigenesis, highlight a possible therapeutic potential of p1932 for the treatment of oral cancer.
authors.affiliation: Dipartimento di Scienze Agrarie Alimentari ed Ambientali, Unità di Ricerca di Biochimica e Biologia Molecolare, Perugia, Italy.
authors.forename: Carlo Alberto
authors.initials: CA
authors.lastname: Palmerini
authors.affiliation: Dipartimento di Scienze Agrarie Alimentari ed Ambientali, Unità di Ricerca di Biochimica e Biologia Molecolare, Perugia, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Mazzoni
authors.affiliation: Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina, Catholic University, Roma, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Radicioni
authors.affiliation: Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina, Catholic University, Roma, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Marzano
authors.affiliation: Dipartimento di Scienze Agrarie Alimentari ed Ambientali, Unità di Ricerca di Biochimica e Biologia Molecolare, Perugia, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Granieri
authors.affiliation: Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina, Catholic University, Roma, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Iavarone
authors.affiliation: Istituto per la Chimica del Riconoscimento Molecolare, Italian National Research Council, Milan, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Longhi
authors.affiliation: Dipartimento di Scienze della Vita e dell'Ambiente, University of Cagliari, Cittadella Universitaria, Monserrato, Cagliari, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Messana
authors.affiliation: Dipartimento di Scienze della Vita e dell'Ambiente, University of Cagliari, Cittadella Universitaria, Monserrato, Cagliari, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cabras
authors.affiliation: Dipartimento di Scienze della Vita e dell'Ambiente, University of Cagliari, Cittadella Universitaria, Monserrato, Cagliari, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Sanna
authors.affiliation: Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina, Catholic University, Roma, Italy.|Istituto per la Chimica del Riconoscimento Molecolare, Italian National Research Council, Rome, UoS Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Castagnola
authors.affiliation: Istituto per la Chimica del Riconoscimento Molecolare, Italian National Research Council, Rome, UoS Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Vitali
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007477:Ions / Q000737:chemistry; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology; D055232:Proline-Rich Protein Domains; D011485:Protein Binding; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D007477:Ions; D008565:Membrane Proteins; C115296:PGRMC1 protein, human; D010455:Peptides; D011372:Progestins; D011980:Receptors, Progesterone; D011374:Progesterone; D002118:Calcium
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