Potent effects of low levels of MHC class II-associated invariant chain on CD4+ T cell development

Naujokas, Marisa F.; Arneson, Lynne S.; Fineschi, Beatrice; Peterson, Mary; Sitterding, Stephanie; Hammond, Adam T.; Reilly, Christina R.; Lo, David; Miller, Jim

doi:10.1016/1074-7613(95)90120-5

Cited by 45 publications

(35 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD44v9, although increased in prostate cancer cells (36), was not increased at the cell surface. Taken together, these data suggest that although CD44 may be necessary for CD74 signaling (21,22), it is not a regulating mechanism because it is present in overabundance and in steady-state levels at the cell surface. Therefore, these results suggest that up-regulation of cell surface CD74 is the necessary step in mediating MIF-CD74-activated signal transduction.…”

Section: Discussionmentioning

confidence: 87%

See 1 more Smart Citation

Inhibition of Macrophage Migration Inhibitory Factor or Its Receptor (CD74) Attenuates Growth and Invasion of DU-145 Prostate Cancer Cells

Meyer-Siegler

Iczkowski

Leng

et al. 2006

The Journal of Immunology

230

220

View full text Add to dashboard Cite

Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, is overexpressed in prostate cancer, but the mechanism by which MIF exerts effects on tumor cells remains undetermined. MIF interacts with its identified membrane receptor, CD74, in association with CD44, resulting in ERK 1/2 activation. Therefore, we hypothesized that increased expression or surface localization of CD74 and MIF overexpression by prostate cancer cells regulated tumor cell viability. Prostate cancer cell lines (LNCaP and DU-145) had increased MIF gene expression and protein levels compared with normal human prostate or benign prostate epithelial cells (p < 0.01). Although MIF, CD74, and CD44 variant 9 expression were increased in both androgen-dependent (LNCaP) and androgen-independent (DU-145) prostate cancer cells, cell surface of CD74 was only detected in androgen-independent (DU-145) prostate cancer cells. Therefore, treatments aimed at blocking CD74 and/or MIF (e.g., inhibition of MIF or CD74 expression by RNA interference or treatment with anti-MIF- or anti-CD74- neutralizing Abs or MIF-specific inhibitor, ISO-1) were only effective in androgen-independent prostate cancer cells (DU-145), resulting in decreased cell proliferation, MIF protein secretion, and invasion. In DU-145 xenografts, ISO-1 significantly decreased tumor volume and tumor angiogenesis. Our results showed greater cell surface CD74 in DU-145 prostate cancer cells that bind to MIF and, thus, mediate MIF-activated signal transduction. DU-145 prostate cancer cell growth and invasion required MIF activated signal transduction pathways that were not necessary for growth or viability of androgen-dependent prostate cells. Thus, blocking MIF either at the ligand (MIF) or receptor (CD74) may provide new, targeted specific therapies for androgen-independent prostate cancer.

show abstract

Section: Discussionmentioning

confidence: 87%

“…Recent studies have identified recruitment of transmembrane CD44 as a potential accessory protein required for MIF-CD74 signal transduction (21,22). In addition, we recently showed the formation of a molecular complex between MIF, CD74, and CD44 in HT-1376 bladder carcinoma cells (23).…”

mentioning

confidence: 98%

Inhibition of Macrophage Migration Inhibitory Factor or Its Receptor (CD74) Attenuates Growth and Invasion of DU-145 Prostate Cancer Cells

Meyer-Siegler

Iczkowski

Leng

et al. 2006

The Journal of Immunology

230

220

View full text Add to dashboard Cite

show abstract

“…The intracytoplasmic portion of CD74 is known to undergo phosphorylation (Ser6, Ser8), in a protein-kinase dependent manner, but evidence supporting ligand activation in this process has not been reported [54]. It nevertheless is noteworthy that recent studies have identified an accessory role for CD74 in T cell stimulation, and by a function that requires a chondroitin-sulphatedependent interaction between CD74 and CD44 [33,34]. CD44 is a widely-expressed, polymorphic transmembrane protein with known tyrosine kinase activation properties [55].…”

Section: How Does Mif Mediate Signal Transduction Through Its Receptor?mentioning

confidence: 99%

“…We sequenced 50 clones and found that the majority encoded CD74, the cell surface form of the Major Histocompatibility Class II-associated invariant chain, that is a 31-41 kDa Type II transmembrane protein (Figure 3). Invariant chain has been well-studied for its role as a Major Histocompatibility Class II chaperone [32], and the cell surface CD74 form has a previously described role in immune cell co-stimulation [33,34]. It is notable that like MIF, cell surface CD74 is expressed as a homotrimer [35].…”

Section: Cloning Of the Mif Receptormentioning

confidence: 99%

Insight into the biology of Macrophage Migration Inhibitory Factor (MIF) revealed by the cloning of its cell surface receptor

Leng

Bucala

2006

Cell Res

View full text Add to dashboard Cite

Abbreviations: Alexa-MIF (Alexa-488-modified MIF); ERK-1/2 (extracellular signal-related kinase); KO (gene knock-out); LPS (lipopolysaccharide); MAPK (mitogen-activated protein kinase); MIF (macrophage migration inhibitory factor); RIP (regulated intramembrane proteolysis); sCD74 (soluble CD74 ectodomain); TLR-4 (Toll-like receptor 4). IntroductionThe protein mediator known as macrophage migration inhibitory factor (MIF) is considered to be one of the first cytokines to be discovered. In the late 1950s, "MIF" described an activity elaborated by activated lymphocytes that arrested the random movement of monocytes/macrophages [1]. This activity correlates with delayed-type hypersensitivity in vitro, and it induced significant interest among immunologists for representing a soluble, but non-immunoglobulin, factor that could be studied and manipulated in vitro. By 1966, John David and Barry Bloom independently described that MIF was most likely a protein that was secreted into the conditioned medium of activated lymphocytes [2,3], and immunologists soon measured MIF's eponymous activity by a capillary tube assay. However, MIF was difficult to isolate or clone, so as various other lymphokines (T cell growth factor/IL-2), monokines (endogenous pyrogen/IL-1; tumor necrosis factor/lymphotoxin), and interferons were systematically cloned and produced recombinantly and additional proteins, such as interferon-g and IL-4, were also observed to exhibit migration inhibitory activity, immunologic interest in MIF waned. It wasn't until 1989 that a discrete gene sequence was determined to be associated with MIF [4] and in 1993, pure recombinant protein became available for biologic and structure-function studies [5]. The threedimensional crystal structure of MIF was solved by three laboratories in 1996, thus revealing a new protein fold and structural superfamily with MIF as its defining member [6][7][8]. These studies also provided insights into the likely native form of the protein -a homotrimer with a MW of 37.5 kDa (Figure 1). Figure 1 Three-dimensional ribbon diagram of human MIF, revealing its homotrimeric subunit structure. From ref [7]. Each color denotes one monomer. Human MIF homotrimerCell Research (2006) The recent cloning of MIF receptor fills an important gap in our understanding of the molecular biology and immunology of MIF. The MIF receptor, like MIF, does not fall into any established family of protein mediators, providing both new challenges and opportunities for the structural and functional analysis of MIF signal transduction.

show abstract

“…In some cases, immunoprecipitates were incubated with endoglycosidase H or N-glycosidase (Roche Applied Science, Indianapolis, IN) as described (39). Western blotting was performed as previously described (40). Blots were incubated with appropriate dilutions of primary Abs, followed by incubation with HRP-conjugated secondary Abs (Amersham Biosciences).…”

Section: Radiolabeling Immunoprecipitation and Western Blotsmentioning

confidence: 99%

Endoplasmic Reticulum-Associated Degradation-Induced Dissociation of Class II Invariant Chain Complexes Containing a Glycosylation-Deficient Form of p41

Sevilla

Comstock

Swier

et al. 2004

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

The quality control system in the secretory pathway can identify and eliminate misfolded proteins through endoplasmic reticulum-associated degradation (ERAD). ERAD is thought to occur by retrotranslocation through the Sec61 complex into the cytosol and degradation by the proteasome. However, the extent of disassembly of oligomeric proteins and unfolding of polypeptide chains that is required for retrotranslocation is not fully understood. In this report we used a glycosylation mutant of the p41 isoform of invariant chain (Ii) to evaluate the ability of ERAD to discriminate between correctly folded and misfolded subunits in an oligomeric complex. We show that loss of glycosylation at position 239 of p41 does not detectably affect Ii trimerization or association with class II but does result in a defect in endoplasmic reticulum export of Ii that ultimately leads to its degradation via the ERAD pathway. Although class II associated with the mutated form of p41 is initially retained in the endoplasmic reticulum, it is subsequently released and traffics through the Golgi to the plasma membrane. ERAD-mediated degradation of the mutant p41 is dependent on mannose trimming and inhibition of mannosidase I stabilizes Ii. Interestingly, inhibition of mannosidase I also results in prolonged association between the mutant Ii and class II, indicating that complex disassembly and release of class II is linked to mannosidase-dependent ERAD targeting of the misfolded Ii. These results suggest that the ERAD machinery can induce subunit disassembly, specifically targeting misfolded subunits to degradation and sparing properly folded subunits for reassembly and/or export.

show abstract

Potent effects of low levels of MHC class II-associated invariant chain on CD4+ T cell development

Cited by 45 publications

References 92 publications

Inhibition of Macrophage Migration Inhibitory Factor or Its Receptor (CD74) Attenuates Growth and Invasion of DU-145 Prostate Cancer Cells

Inhibition of Macrophage Migration Inhibitory Factor or Its Receptor (CD74) Attenuates Growth and Invasion of DU-145 Prostate Cancer Cells

Insight into the biology of Macrophage Migration Inhibitory Factor (MIF) revealed by the cloning of its cell surface receptor

Endoplasmic Reticulum-Associated Degradation-Induced Dissociation of Class II Invariant Chain Complexes Containing a Glycosylation-Deficient Form of p41

Contact Info

Product

Resources

About