Regulation of mTORC1 Complex Assembly and Signaling by GRp58/ERp57

Ramírez-Rangel, Iliana; Bracho-Valdés, Ismael; Vázquez-Macías, Aleida; Carretero‐Ortega, Jorge; Reyes‐Cruz, Guadalupe; Vázquez‐Prado, José

doi:10.1128/mcb.00824-10

Cited by 58 publications

(71 citation statements)

References 56 publications

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“…The ERp57-Ref-1 complex, furthermore, shuttles between the cytosol and the nucleus, where the reduction of transcription factors is expected to take place. Further evidence of the importance of ERp57 as a redox-sensing protein involved in regulatory processes has resulted from a very recent study, showing the interaction of ERp57 with mTOR [64], taking place in the cytosol and on the cytosolic side of the ER membrane. mTOR is a serine-threonine protein kinase, found in two multiprotein complexes called mTORC1 and mTORC2.…”

Section: Erp57 In the Cytosolmentioning

confidence: 99%

“…It appears that at least part of this behavior is related to the mTOR-ERp57 interaction, considering that mTOR is involved in the regulation of proliferation. mTORC1 was previously shown to be redox-regulated [65], and ERp57 can now be held responsible for this redox dependence [64]. mTOR is a known inhibitor of autophagy, and its activity is inhibited by starvation, with consequent stimulation of the autophagic process.…”

Section: Erp57 In the Cytosolmentioning

confidence: 99%

“…Thus, the intervention of ERp57 in mTOR redox regulation might suggest the involvement of ERp57 in autophagy. ERp57 also interacts with mTORC2, although no significant functional alterations of this complex have been reported [64].…”

Section: Erp57 In the Cytosolmentioning

confidence: 99%

“…Internalization and nuclear import [43-44, 46, 49] Regulation of bone-related gene transcription and mineralization in osteoblast-like MC3T3-E1 cells [45] Interaction with the angiotensin II receptor [50] Interaction with vasopressin receptor [51] Interaction with the all-trans retinoic acid receptor α [55] Interaction with STAT3 in the lipid raft fraction of cell membrane Participation of a signal transduction pathway initiating at the cell surface [57,58] Cytosol Interaction with STAT3 in the cytosol Present in a multiprotein complex [56][57][58]78] Interaction with the all-trans retinoic acid receptor α Transport of the ligand-receptor complex into the nucleus (in the Sertoli cells) [55] Interaction with NFκB in the cytosol of leukemic cells [49] Redox activity; interaction with Maintenance of the reduced state of Ref-1 (complex, shuttles between the cytosol and the nucleus) [13] Interaction with mTOR Assembly and functioning of the multiprotein complex mTORC1; Appears to be at least in part responsible for the redox dependence of mTORC1 activity [64] Nucleus Redox activity; interaction with Ref-…”

Section: Endoplasmic Reticulummentioning

confidence: 99%

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ERp57/GRP58: A protein with multiple functions

Turano

Gaucci

Grillo

et al. 2011

Cellular and Molecular Biology Letters

114

108

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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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Section: Erp57 In the Cytosolmentioning

confidence: 99%

Section: Erp57 In the Cytosolmentioning

confidence: 99%

Section: Erp57 In the Cytosolmentioning

confidence: 99%

Section: Endoplasmic Reticulummentioning

confidence: 99%

See 2 more Smart Citations

ERp57/GRP58: A protein with multiple functions

Turano

Gaucci

Grillo

et al. 2011

Cellular and Molecular Biology Letters

114

108

View full text Add to dashboard Cite

show abstract

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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SUMMARYHypogonadism is defined as the inadequate gonadal production of testosterone. Low serum testosterone leads to infertility by impairing spermatogenesis and reducing sperm count, however, the impact of hypogonadism in epididymal sperm maturation is poorly understood. From the testis, spermatozoa are transported into the epididymis where they find a specific microenvironment composed of a complex mixture of proteins that facilitate sperm storage and maturation. Inside the epididymal ductule, spermatozoa undergo several changes, resulting in their becoming capable of fertilizing eggs. Protein disulfide isomerases (PDIs) are known to participate in the folding and assembly of secreted proteins in the endoplasmic reticulum. However, little is known about the control and function of PDIs in the testis and epididymis, particularly during male development. The aim of this work was to compare the expression and distribution of PDI and PDIA3 (ERp57) in the testis and epididymis of healthy and GnRH-immunized boars. We detected higher amounts of PDIA3 and PDI in sperm preparations and fluid from the proximal regions of the epididymis of healthy boars. However, we observed an increase in PDIA3 expression in the testis and cauda epididymis in the immunocastrated group. GnRH-immunized boars showed a marked increase in PDI content in cauda spermatozoa and fluid, indicating a possible endocrine dysregulation of PDI. The results of our study suggest that PDIs are associated with epididymal sperm maturation and may be attractive candidates for monitoring male fertility.

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mTORC1‐ and mTORC2‐interacting proteins keep their multifunctional partners focused

et al. 2011

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SummaryThe mammalian target of rapamycin, best known as mTOR, is a phylogenetically conserved serine/threonine kinase that controls life-defining cellular processes such as growth, metabolism, survival, and migration under the influence of multiple interacting proteins. Historically, the cellular activities blocked by rapamycin in mammalian cells were considered the only events controlled by mTOR. However, this paradigm changed with the discovery of two signaling complexes differentially sensitive to rapamycin, whose catalytic component is mTOR. The one sensitive to rapamycin, known as mTORC1, promotes protein synthesis in response to growth factors and nutrients via the phosphorylation of p70S6K and 4EBP1; while the other, known as mTORC2, promotes cell migration and survival via the activation of Rho GTPases and the phosphorylation of AKT, respectively. Although mTORC2 kinase activity is not inhibited by rapamycin, hours of incubation with this antibiotic can impede the assembly of this signaling complex. The direct mechanism by which mTORC2 leads to cell migration depends on its interaction with PRex1, a Rac-specific guanine nucleotide exchange factor, while additional indirect pathways involve the intervention of PKC or AKT, multifunctional ubiquitous serine/threonine kinases that activate effectors of cell migration upon being phosphorylated by mTORC2 in response to chemotactic signals. These mTORC2 effectors are altered in metastatic cancer. Numerous clinical trials are testing mTOR inhibitors as potential antineoplasic drugs. Here, we briefly review the actions of mTOR with emphasis on the controlling role of mTORC1 and mTORC2-interacting proteins and highlight the mechanisms linked to cell migration.

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Regulation of mTORC1 Complex Assembly and Signaling by GRp58/ERp57

Cited by 58 publications

References 56 publications

ERp57/GRP58: A protein with multiple functions

ERp57/GRP58: A protein with multiple functions

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

mTORC1‐ and mTORC2‐interacting proteins keep their multifunctional partners focused

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