LMP2 expression and proteasome activity in NOD mice

Runnels, Herbert A.; Watkins, Wendy A.; Monaco, John J.

doi:10.1038/80349

Cited by 25 publications

(28 citation statements)

References 14 publications

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“…(Kessler et al, 2000;Runnels et al, 2000). Moreover, a reconstitution of T2 cells with LMP2 and/or LMP7 did not change the quantity of the mature p50 subunit of NF-B (Runnels et al, 2000). The follow-up study by Hayashi and Faustman also found reduced IB␣ degradation in LMP2 −/− lymphocytes upon stimulation with TNF-␣ (Hayashi and Faustman, 2000).…”

Section: Discussionmentioning

confidence: 68%

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Immunoproteasome subunit deficiency has no influence on the canonical pathway of NF-κB activation

Bitzer

Basler

Krappmann

et al. 2017

Molecular Immunology

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a b s t r a c tActivation of the pro-inflammatory transcription factor NF-B requires signal-induced proteasomal degradation of the inhibitor of NF-B (IB) in order to allow nuclear translocation. Most cell types are capable of expressing two types of 20S proteasome core particles, the constitutive proteasome and immunoproteasome. Inducible under inflammatory conditions, the immunoproteasome is mainly characterized through an altered cleavage specificity compared to the constitutive proteasome. However, the question whether immunoproteasome subunits affect NF-B signal transduction differently from constitutive subunits is still up for debate. To study the effect of immunoproteasomes on LPS-or TNF-␣-induced NF-B activation, we used IFN-␥ stimulated peritoneal macrophages and mouse embryonic fibroblasts derived from mice deficient for the immunoproteasome subunits low molecular mass polypeptide (LMP) 2, or LMP7 and multicatalytic endopeptidase complex-like 1 (MECL-1). Along the canonical signaling pathway of NF-B activation no differences in the extent and kinetic of IB degradation were observed. Neither the nuclear translocation and DNA binding of NF-B nor the production of the NF-B dependent cytokines TNF-␣, IL-6, and IL-10 differed between immunoproteasome deficient and proficient cells. Hence, we conclude that immunoproteasome subunits have no specialized function for canonical NF-B activation.

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Section: Discussionmentioning

confidence: 68%

“…However, two independent groups could not confirm a lower expression of LMP2 mRNA or protein in NOD as compared to BALB/c splenocytes. (Kessler et al, 2000;Runnels et al, 2000). Moreover, a reconstitution of T2 cells with LMP2 and/or LMP7 did not change the quantity of the mature p50 subunit of NF-B (Runnels et al, 2000).…”

Section: Discussionmentioning

confidence: 90%

Immunoproteasome subunit deficiency has no influence on the canonical pathway of NF-κB activation

Bitzer

Basler

Krappmann

et al. 2017

Molecular Immunology

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“…Although our current data do not agree with these findings, it is possible that the degradation IB␣ or IB␤ is preferentially reduced due to a defect in the LMP2-deficient proteasome. However, others have questioned whether NOD splenocytes do, in fact, exhibit reduced levels of LMP2 (43,44). We are currently exploring whether a defect in LMP2 in NOD DCs affects DC function.…”

Section: Discussionmentioning

confidence: 99%

Dendritic Cells from Nonobese Diabetic Mice Exhibit a Defect in NF-κB Regulation Due to a Hyperactive IκB Kinase

Weaver¹,

Poligone

Bui³

et al. 2001

The Journal of Immunology

117

107

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Insulin-dependent diabetes mellitus (IDDM) is characterized by the T cell-mediated destruction of insulin-producing β cells. Accordingly, APCs, such as macrophage, have also been shown to be important in the disease process. However, the role(s) of dendritic cells (DCs) that exhibit potent APC function remains undefined in IDDM. Here we demonstrate that DCs derived from nonobese diabetic (NOD) mice, a model for IDDM, are more sensitive to various forms of stimulation compared with those from C57BL/6 and BALB/c mice, resulting in increased IL-12 secretion. This property is a consequence of hyperactivation of NF-κB, a transcription factor known to regulate IL-12 gene expression. Specifically, NOD DCs exhibit persistent hyperactivation of both IκB kinase and NF-κB in response to stimuli, in addition to selective degradation of IκBε. Transfection of NOD DCs with a modified form of IκBα significantly reduced IL-12 secretion, suggesting that hyperactivation of NF-κB was in part responsible for increased IL-12 production. An enhanced capacity of NOD DCs to secrete IL-12 would be expected to contribute to the development of pathogenic Th1 (Tc1) cells during the diabetogenic response.

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“…However according to other authors, diabetic rats have higher rates of proteolysis when compared with non-diabetic rats [27,28] as a result of hypoinsulinemia-induced activation of UPS. In contrast to Runnels et al [29], Hayasi and Faustman [30] revealed the presence of a specific proteasome defect in non-obese, diabetic mice. In the present study the relationship between diabetes-induced oxidative stress and proteasomal activity was examined in alloxan-treated rats.…”

Section: Discussionmentioning

confidence: 85%

Proteasome activity in experimental diabetes

2006

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Numerous studies have indicated that oxidative stress contributes to the development and progression of diabetes and other related complications. Since the ubiquitin-proteasome pathway is involved in degradation of oxidized proteins, it is to be expected that alterations in proteasomedependent proteolysis accompany diabetes. This paper focuses on the role of the proteasome in alloxaninduced experimental diabetes. The changes in proteasomal activity and oxidative stress indices (protein oxidation and lipid peroxidation) were evaluated. The obtained results revealed increased protein oxidation and lipid peroxidation, as well as alterations in proteasomal activities in diabetic rats. Our data indicates a significant decrease in chymotryptic-like activity; increased tryptic-like activity; and unchanged post-glutamyl peptide hydrolytic-like activity. These findings suggest the presence of oxidative stress in diabetes that appears to result in changes to the ubiquitin-proteasome pathway.

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LMP2 expression and proteasome activity in NOD mice

Cited by 25 publications

References 14 publications

Immunoproteasome subunit deficiency has no influence on the canonical pathway of NF-κB activation

Immunoproteasome subunit deficiency has no influence on the canonical pathway of NF-κB activation

Dendritic Cells from Nonobese Diabetic Mice Exhibit a Defect in NF-κB Regulation Due to a Hyperactive IκB Kinase

Proteasome activity in experimental diabetes

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