Abbreviations used: 1α,25-(OH) 2 D 3 -1α,25-dihydroxycholecalciferol and calcitriol; APE/Ref-1 -apurinic (apyrimidinic) endonuclease/redox-factor 1; CRP -C-reactive protein; ER -endoplasmic reticulum; ERAD endoplasmic reticulum associated protein degradation; mTORC -mammalian target of rapamycin complex; PDI -protein disulfide isomerase; PKC -protein kinases C; PLA 2 -phospholipases A 2 ; Plc -peptide loading complex; PLC -phospholipase C; PrP SC -scrapie prion protein (misfolded prions); STAT -signal transducer and activator of transcription; STAT3 -signal transducer and activator of transcription 3; SV40 virus -simian virus 40; VDR -vitamin D receptor Review ERp57/GRP58: A PROTEIN WITH MULTIPLE FUNCTIONSCARLO TURANO*, ELISA GAUCCI, CATERINA GRILLO and SILVIA CHICHIARELLI Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Sapienza -Università di Roma, Italy Abstract: The protein ERp57/GRP58 is a stress-responsive protein and a component of the protein disulfide isomerase family. Its functions in the endoplasmic reticulum are well known, concerning mainly the proper folding and quality control of glycoproteins, and participation in the assembly of the major histocompatibility complex class 1. However, ERp57 is present in many other subcellular locations, where it is involved in a variety of functions, primarily suggested by its participation in complexes with other proteins and even with DNA. While in some instances these roles need to be confirmed by further studies, a great number of observations support the participation of ERp57 in signal transduction from the cell surface, in regulatory processes taking place in the nucleus, and in multimeric protein complexes involved in DNA repair.

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Self-assembled nanohydrogels based on hydrophobically modified polysaccharides have been extensively studied due to their wide potential applications as drug delivery systems. In the present study, we developed and characterized self-assembling nanohydrogels based on sonicated gellan gum chains. Prednisolone (Pred), a poorly water soluble anti-inflammatory drug, was chemically conjugated to the carboxylic groups of gellan (Ge-Pred) and it was the hydrophobic moiety responsible for the self-assembling process. Ge-Pred was characterized by proton nuclear magnetic resonance spectra (H-1-NMR) and the cellular cytotoxicity was assessed by the MTS assay. The self-aggregation behavior in aqueous media of Ge-Pred was evaluated by the pyrene fluorescence technique and the nanohydrogels (NHs), prepared by bath sonication in water, were analyzed by dynamic light scattering (DLS) and zeta-potential. The average size of the nanohydrogels was about 300 nm and their zeta-potential values were negative. Our results showed that Ge-Pred NHs are cytocompatible, that the drug is bioavailable and, consequently, they represent an interesting and innovative carrier for prednisolone

The disulfide isomerase ERp57 is a soluble protein mainly located in the endoplasmic reticulum, where it acts in the quality control of newly synthesized glycoproteins, in association with calreticulin and calnexin. It has been also detected in other cell compartments, such as the cytosol, the plasma membrane and the nucleus. In these locations it is implicated in various processes, participating in the rapid response to calcitriol, modulating the activity of STAT3 and being requested for the pre-apoptotic exposure of calreticulin on the plasma membrane. In the present work, the involvement of ERp57 in the activity of the EGF receptor was evaluated for the first time. EGFR is a tyrosine kinase receptor, which is able to activate numerous signaling cascades, leading to cell proliferation and inhibition of apoptosis. In the MDA-MB-468 breast adenocarcinoma cells, which overexpress EGFR, ERp57 expression has been knocked down by siRNA and the effects on EGFR have been studied. ERp57 silencing did not affect EGFR protein expression, cell membrane exposure or EGF binding, whereas the internalization and the phosphorylation of the receptor were impaired. The implication of ERp57 in the activity of EGFR, whose upregulation is known to be associated with tumors, could be relevant for cancer therapy.