title: ERp57/PDIA3 binds specific DNA fragments in a melanoma cell line.
abstract: ERp57/PDIA3 is a ubiquitously expressed disulfide isomerase protein, which acts in concert with calreticulin and calnexin in the folding of glycoproteins destined to the plasma membrane or to be secreted. Its canonical compartment is the endoplasmic reticulum, where it acts as a chaperone and redox catalyst, but non canonical locations have been described as well, and ERp57 has been found associated with DNA and nuclear proteins. In previous work performed in HeLa cells, ERp57 has been demonstrated to bind specific DNA sequences involved in the stress response. The direct interaction with the DNA sequences identified as ERp57-targeted regions in HeLa cells has now been confirmed in a melanoma cell line. Furthermore, the ERp57 silencing, achieved by RNA interference, has produced a significant down-regulation of the expression of target genes. The possible involvement of other proteins in complex with ERp57 has been studied by an in vitro biotin-streptavidin based binding assay and the interacting protein APE/Ref-1 has been also assessed for its direct association with the ERp57 target regions. In conclusion, nuclear ERp57 interacts in vivo with DNA fragments in melanoma cells and is potentially involved in the transcriptional regulation of its target genes.
authors.affiliation: Department of Biochemical Sciences "A. Rossi Fanelli", "Sapienza" University of Rome, Piazzale Aldo Moro 5, Rome 00185, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Aureli
authors.forename: Elisa
authors.initials: E
authors.lastname: Gaucci
authors.forename: Valentina
authors.initials: V
authors.lastname: Arcangeli
authors.forename: Caterina
authors.initials: C
authors.lastname: Grillo
authors.forename: Margherita
authors.initials: M
authors.lastname: Eufemi
authors.forename: Silvia
authors.initials: S
authors.lastname: Chichiarelli
mesh_terms: D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D002945:Cisplatin / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases / Q000235:genetics* / Q000378:metabolism; D025941:Protein Interaction Mapping; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human; D002945:Cisplatin