Ubiquitin C-Terminal Hydrolase L1 is required for regulated protein degradation through the ubiquitin proteasome system in kidney

Radón, Victoria; Czesla, Maire; Reichelt, Julia; Fehlert, Julia; Hammel, Anna; Rosendahl, Alva; Knop, Jan-Hendrik; Wiech, Thorsten; Wenzel, Ulrich; Sachs, Marlies; Reinicke, Anna T.; Stahl, Rolf A.K.; Meyer-Schwesinger, Catherine

doi:10.1016/j.kint.2017.05.016

Cited by 25 publications

(19 citation statements)

References 48 publications

(62 reference statements)

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“…UCH-L1 is expressed in DCs, and its expression and enzymatic activity is regulated by LPS and IFN-g stimulation UCH-L1 is one of the most abundant proteins found in the mammalian brain and is also highly expressed in the peripheral nervous system (24,25). We have previously shown that UCH-L1 is expressed in glomerular and tubulointerstitial cells of the kidney closely resembling DCs (16). This study focuses on the novel expression of UCH-L1 in DCs and its impact on the immune response.…”

Section: Resultsmentioning

confidence: 99%

“…UCH-L1 complete knockout animals on C57BL/6 background were generated (16) and bred at our animal facility. Both wild-type and heterozygous littermates were used as control group.…”

Section: Animals and Listeria Monocytogenes Infection Modelmentioning

confidence: 99%

“…We recently described the expression of UCH-L1 in tubulointerstitial cells of the kidney of nonvascular origin, which phenotypically resemble DCs (16). We showed that UCH-L1deficient mice exhibit an altered course of immune complex glomerulonephritis, and therefore, we wished to investigate whether UCH-L1 plays a role in the immune response.…”

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confidence: 99%

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Deubiquitinating Enzyme UCH-L1 Promotes Dendritic Cell Antigen Cross-Presentation by Favoring Recycling of MHC Class I Molecules

Reinicke

Raczkowski

Mühlig

et al. 2019

The Journal of Immunology

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The deubiquitinating enzyme ubiquitin C-terminal hydrolase-L1 (UCH-L1) is required for the maintenance of axonal integrity in neurons and is thought to regulate the intracellular pool of ubiquitin in the brain. In this study, we show that UCH-L1 has an immunological function in dendritic cell (DC) Ag cross-presentation. UCH-L1 is expressed in mouse kidney, spleen, and bone marrow-derived DCs, and its expression and activity are regulated by the immune stimuli LPS and IFN-g. UCH-L1-deficient mice have significantly reduced ability to cross-prime CD8 T cells in vivo and in vitro because of a reduced ability of DCs to generate MHC class I (MHC I) peptide complexes for cross-presented Ags. Mechanistically, Ag uptake by phagocytosis and receptor-mediated endocytosis as well as phagosome maturation are unaffected by loss of UCH-L1 in DCs. Rather, MHC I recycling is reduced by loss of UCH-L1, which affects the colocalization of intracellular MHC I with late endosomal/lysosomal compartments necessary for cross-presentation of Ag. These results demonstrate a hitherto unrecognized role of the deubiquitinating enzyme UCH-L1 in DC Ag processing.

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Section: Resultsmentioning

confidence: 99%

“…UCH-L1 complete knockout animals on C57BL/6 background were generated (16) and bred at our animal facility. Both wild-type and heterozygous littermates were used as control group.…”

Section: Animals and Listeria Monocytogenes Infection Modelmentioning

confidence: 99%

See 1 more Smart Citation

Deubiquitinating Enzyme UCH-L1 Promotes Dendritic Cell Antigen Cross-Presentation by Favoring Recycling of MHC Class I Molecules

Reinicke

Raczkowski

Mühlig

et al. 2019

The Journal of Immunology

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“…In the current study, Peak 2682 was repeated in Group I-III. This mass is believed to be ubiquitin Cterminal hydrolase L1 protein [14], this protein was found to be expressed in human kidney podocytes; it was found that it is important for protein degradation in the human kidney, so it may have a role in pathogenesis of graft dysfunction, it needs further studies to prove this relation [15].…”

Section: Discussionmentioning

confidence: 99%

Identification of urinary proteomic profile of patients with chronic allograft nephropathy

Hussien

Moez

El-Wakil

et al. 2020

Alexandria Journal of Medicine

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Background and objectives: Chronic allograft nephropathy (CAN) is a major complication that occurs post-transplantation. At present, the diagnosis of CAN is based on renal biopsy. Therefore, there is an ultimate need to identify more specific and sensitive noninvasive methods for the early diagnosis of CAN. Recently, proteomic-based modalities have been developed to discover biomarkers of CAN. Methods: Urine samples from 75 participants were collected. Participants were divided into three groups: Group I: 25 patients with CAN, Group II: 25 transplanted patients with stable renal functions, and Group III: 25 healthy control subjects matched for age and sex. Each group was divided into training set and test set. Specimens were purified with magnetic beads-based weak cation exchange chromatography and analyzed using MALDI-TOF MS. Results: A Genetic Algorithm (GA) was used to set up the classification models. Five peaks represented the proteomic profile that differentiates between the CAN patients and the control group with sensitivity of 100%, specificity of 100%, recognition capability of 100%, and crossvalidation of 91.7% and five peaks differentiate between the transplant patients with normal renal functions and the control groups with sensitivity of 96.8%, specificity of 95.5%, recognition capability of 98%, and cross-validation of 100%. Interpretation and conclusions: We identified a pattern for CAN and transplant patients with normal renal functions by proteomic profiling using MALDI-TOF-MS and magnetic beads.

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“…NFκB increases UCH-L1 expression in podocytes, which plays a role in immune complex-mediated, but not in non-immune complex-mediated, GN (75, 76). UCH-L1 knockout mice have an exacerbation of kidney injury, probably through the decline of proteasomal activity and the increase in oxidative-modified and polyubiquitinated proteins (77). Disruption of ABIN1, another deubiquitinating enzyme, increases the severity of GN through the increased activation of NFκB in podocytes (78).…”

Section: Renal Disease—glomerulonephritismentioning

confidence: 99%

NFκB and Kidney Injury

2019

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The global burden of chronic kidney disease will increase during the next century. As NFκB, first described more than 30 years ago, plays a major role in immune and non-immune-mediated diseases and in inflammatory and metabolic disorders, this review article summarizes current knowledge on the role of NFκB in in vivo kidney injury and describes the new and so far not completely understood crosstalk between canonical and non-canonical NFκB pathways in T-lymphocyte activation in renal disease.

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Ubiquitin C-Terminal Hydrolase L1 is required for regulated protein degradation through the ubiquitin proteasome system in kidney

Cited by 25 publications

References 48 publications

Deubiquitinating Enzyme UCH-L1 Promotes Dendritic Cell Antigen Cross-Presentation by Favoring Recycling of MHC Class I Molecules

Deubiquitinating Enzyme UCH-L1 Promotes Dendritic Cell Antigen Cross-Presentation by Favoring Recycling of MHC Class I Molecules

Identification of urinary proteomic profile of patients with chronic allograft nephropathy

NFκB and Kidney Injury

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