title: The binding of silibinin to ERp57.
abstract: The flavonoid silibinin is known to intervene in many cellular processes involved in a variety of pathologies, thus appearing a promising therapeutic tool. The molecular mechanisms responsible for these activities, however, have not been clearly defined, and although some of its interactions with proteins have been identified, the relative affinities are often too low to appear relevant in vivo. Here we describe the interaction of silibinin with the protein disulfide isomerase ERp57, characterized by a submicromolar dissociation constant. This interaction enhances the formation of a ERp57/REF-1 complex, and furthermore appears to affect the intracellular distribution of ERp57. This protein is involved in signaling pathways which are also affected by silibinin. This suggests that the ERp57-silibinin interaction might explain at least some of the biological effects caused by the flavonoid.
authors: Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy; Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors: Caterina
authors: C
authors: Grillo
authors: Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors: Silvia
authors: S
authors: Chichiarelli
authors: Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors: Elisa
authors: E
authors: Gaucci
authors: Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy; Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors: Fabio
authors: F
authors: Altieri
authors: Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors: Carlo
authors: C
authors: Turano
authors: Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy. Electronic address: laura.cervoni@uniroma1.it.
authors: Laura
authors: L
authors: Cervoni
mesh_terms: D002151:Calorimetry; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D011485:Protein Binding / Q000502:physiology; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism*; D000077385:Silybin; D012838:Silymarin / Q000378:metabolism*
chemical_list: D008024:Ligands; D012838:Silymarin; D000077385:Silybin; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human
keywords: ERp57; Protein ligand interaction; Ref1; STAT3; Silibinin