ERp57 Modulates STAT3 Signaling from the Lumen of the Endoplasmic Reticulum

Coe, Helen; Jung, Joanna; Groenendyk, Jody; Prins, Daniel; Michalak, Marek

doi:10.1074/jbc.m109.054015

Cited by 100 publications

(99 citation statements)

References 60 publications

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“…Knockout mice models also elucidate specific and redundant functions of ER oxidoreductases. For example, ERp57 knockout mice showed embryonic lethality, suggesting that ERp57 has a specific role in early development (Garbi et al 2006;Coe et al 2010). Knockout mice of ERdj5, Prdx4, and Ero1a/b (see later section) showed less severe phenotypes, which suggests that their roles can be compensated for by other factors (Iuchi et al 2009;Hosoda et al 2010;Zito et al 2010a).…”

Section: Disulfide Bond Formationmentioning

confidence: 99%

Protein Folding and Quality Control in the ER

Araki

Nagata

2011

Cold Spring Harbor Perspectives in Biology

326

285

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The endoplasmic reticulum (ER) uses an elaborate surveillance system called the ER quality control (ERQC) system. The ERQC facilitates folding and modification of secretory and membrane proteins and eliminates terminally misfolded polypeptides through ER-associated degradation (ERAD) or autophagic degradation. This mechanism of ER protein surveillance is closely linked to redox and calcium homeostasis in the ER, whose balance is presumed to be regulated by a specific cellular compartment. The potential to modulate proteostasis and metabolism with chemical compounds or targeted siRNAs may offer an ideal option for the treatment of disease.

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Section: Disulfide Bond Formationmentioning

confidence: 99%

Protein Folding and Quality Control in the ER

Araki

Nagata

2011

Cold Spring Harbor Perspectives in Biology

326

285

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“…STAT3 signaling is dependent on ERp57, which modulates its activity by ER luminal interactions (53). Moreover, ERp57 aberrant expression in carcinomas is a prognostic factor (54).…”

Section: Discussionmentioning

confidence: 99%

A Transcriptome-proteome Integrated Network Identifies Endoplasmic Reticulum thiol oxidoreductase (ERp57) as a Hub that Mediates Bone Metastasis

Santana-Codina

Carretero

Sanz‐Pamplona

et al. 2013

Molecular & Cellular Proteomics

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Bone metastasis is the most common distant relapse in breast cancer. The identification of key proteins involved in the osteotropic phenotype would represent a major step toward the development of new prognostic markers and therapeutic improvements. The aim of this study was to characterize functional phenotypes that favor bone metastasis in human breast cancer. We used the human breast cancer cell line MDA-MB-231 and its osteotropic BO2 subclone to identify crucial proteins in bone metastatic growth. We identified 31 proteins, 15 underexpressed and 16 overexpressed, in BO2 cells compared with parental cells. We employed a network-modeling approach in which these 31 candidate proteins were prioritized with respect to their potential in metastasis formation, based on the topology of the protein-protein interaction network and differential expression. The protein-protein interaction network provided a framework to study the functional relationships between biological molecules by attributing functions to genes whose functions had not been characterized. The combination of expression profiles and protein interactions revealed an endoplasmic reticulum-thiol oxidoreductase, ERp57, function- Large-scale genomic analysis has provided a wealth of information on biologically relevant systems, and the ability to analyze this information is crucial to uncovering important biological relationships. In breast cancer, microarray gene expression analysis is a promising technique for providing consistent patterns of variation in bone metastasis gene expression; the most common metastasis (80%) in those women who progress to an advanced stage of disease (1-4). However, a large number of genes with many diverse functions are identified as prognostic markers, without revealing much about the underlying biological mechanism.Genes that enhance or suppress bone metastasis are associated with multiple cellular processes that normally occur during metastasis progression, including survival and proliferation in the bone marrow microenvironment, and modification of bone structure and function (1). Many genes in this group encode secretory or cell surface proteins involved in cell homing to bone, angiogenesis, invasion, and osteoclast recruitment (1, 2, 5). Moreover, emerging evidence from murine models suggests that tumor-specific endocrine factors systematically stimulate the quiescent bone marrow compartment (BM), resulting in a BM-derived tumor microenvironment From the ‡Biological Clues

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“…(26)(27)(28)(29) Here, we sought to elucidate the physiological role of ERp57 in postnatal bone growth in mice. Because constitutive ERp57 knockout (KO) mice show embryonic lethality at E13.5, (20,30,31) we analyzed mice with a targeted ablation of the ERp57 gene in chondrocytes. Because the growth characteristics differ between the sexes, growing male and female mice were investigated separately.…”

Section: Introductionmentioning

confidence: 99%

ER Stress During the Pubertal Growth Spurt Results in Impaired Long-Bone Growth in Chondrocyte-Specific ERp57 Knockout Mice

Linz

Knieper

Gronau

et al. 2015

Journal of Bone and Mineral Research

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Long-bone growth by endochondral ossification is cooperatively accomplished by chondrocyte proliferation, hypertrophic differentiation, and appropriate secretion of collagens, glycoproteins, and proteoglycans into the extracellular matrix (ECM). Before folding and entering the secretory pathway, ECM macromolecules in general are subject to extensive posttranslational modification, orchestrated by chaperone complexes in the endoplasmic reticulum (ER). ERp57 is a member of the protein disulfide isomerase (PDI) family and facilitates correct folding of newly synthesized glycoproteins by rearrangement of native disulfide bonds. Here, we show that ERp57-dependent PDI activity is essential for postnatal skeletal growth, especially during the pubertal growth spurt characterized by intensive matrix deposition. Loss of ERp57 in growth plates of cartilage-specific ERp57 knockout mice (ERp57 KO) results in ER stress, unfolded protein response (UPR), reduced proliferation, and accelerated apoptotic cell death of chondrocytes. Together this results in a delay of long-bone growth with the following characteristics: (1) enlarged growth plates; (2) expanded hypertrophic zones; (3) retarded osteoclast recruitment; (4) delayed remodeling of the proteoglycan-rich matrix; and (5) reduced numbers of bone trabeculae. All the growth plate and bone abnormalities, however, become attenuated after the pubertal growth spurt, when protein synthesis is decelerated and, hence, ERp57 function is less essential.

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ERp57 Modulates STAT3 Signaling from the Lumen of the Endoplasmic Reticulum

Cited by 100 publications

References 60 publications

Protein Folding and Quality Control in the ER

Protein Folding and Quality Control in the ER

A Transcriptome-proteome Integrated Network Identifies Endoplasmic Reticulum thiol oxidoreductase (ERp57) as a Hub that Mediates Bone Metastasis

ER Stress During the Pubertal Growth Spurt Results in Impaired Long-Bone Growth in Chondrocyte-Specific ERp57 Knockout Mice

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