ERp57/GRP58: A protein with multiple functions

Abstract

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.

A genetic view of laryngeal cancer heterogeneity

“…72 ERp57 (GRP58) is a chaperone that regulated proper folding of glycoproteins. 73 ERp57 is associated with tumor progression ans has been described to modulate STAT 3 activity, thus regulating radioresistance in laryngeal cancer. 74 Accordingly, ERp57 has been described as a poor prognosis factor.…”

The Protein-disulfide Isomerase ERp57 Regulates the Steady-state Levels of the Prion Protein

“…Beside its role in the CNX and CRT cycle, ERp57 is required as a scaffold protein for the assembly of the heavy chain of the MHC class I peptide loading complex, a function independent of its enzymatic activity involving covalent bonding with tapasin (37-39). Additional functions for ERp57 are reported, including the modulation of ER calcium homeostasis and STAT3 signaling (34,40,41). Although PDIs have been proposed to have neuroprotective activities (30), a drug screening identified a proapoptotic role of ERp57 and PDIA1 in models of neurodegeneration (42).…”

GnRH immunization alters the expression and distribution of protein disulfide isomerases in the epididymis

“…It was demonstrated recently that the amount of PDIA3 is reduced in the spermatozoa of male individuals with obesity-associated asthenozoospermia (Liu et al, 2015). Interestingly, PDIA3 also binds to the hydroxylated, hormonal form of vitamin D3,1a,25-dihydroxycholecalciferol (1a,25-(OH)2D3, calcitriol), and therefore may be involved in hormonal signaling processes (Nemere et al, 2004;Turano et al, 2011). This pathway activates numerous signal transduction cascades, such as protein kinase C (PKC), phospholipases C (PLC) and A2 (PLA2), and extracellular response activated kinase (ERK), all of which have been shown to respond to the formation of the PDIA3-1a,25-(OH)2D3 complex (Boyan et al, 2007;Chen et al, 2010).…”

“…Although the main function of PDIA3 is to mediate the folding and quality control of newly synthesized glycoproteins in the endoplasmic reticulum (Coe & Michalak, 2010;Turano et al, 2011), it has also been found in other subcellular locations, such as in the nucleus, cytoplasm, and at the cell surface. Some studies have suggested that PDIA3 participates in transcriptional regulation (Coppari et al, 2002), signal transduction Ramirez-Rangel et al, 2011), membrane fusion (Schelhaas et al, 2007), hormone responses (Tunsophon & Nemere, 2010), and sperm-egg fusion (Liu et al, 2014).…”