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

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

doi:10.1016/j.kint.2017.05.016

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

Standard

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 O; Sachs, Marlies; Reinicke, Anna T ; Stahl, Rolf A K ; Meyer-Schwesinger, Catherine.

In: KIDNEY INT, Vol. 93, No. 1, 01.2018, p. 110-127.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Radón, V, Czesla, M, Reichelt, J, Fehlert, J, Hammel, A, Rosendahl, A, Knop, J-H, Wiech, T , Wenzel, UO, Sachs, M, Reinicke, AT , Stahl, RAK & Meyer-Schwesinger, C 2018, 'Ubiquitin C-Terminal Hydrolase L1 is required for regulated protein degradation through the ubiquitin proteasome system in kidney', KIDNEY INT, vol. 93, no. 1, pp. 110-127. https://doi.org/10.1016/j.kint.2017.05.016

APA

Radón, V., Czesla, M., Reichelt, J., Fehlert, J., Hammel, A., Rosendahl, A., Knop, J-H., Wiech, T., Wenzel, U. O., Sachs, M., Reinicke, A. T., Stahl, R. A. K., & Meyer-Schwesinger, C. (2018). Ubiquitin C-Terminal Hydrolase L1 is required for regulated protein degradation through the ubiquitin proteasome system in kidney. KIDNEY INT, 93(1), 110-127. https://doi.org/10.1016/j.kint.2017.05.016

Vancouver

Radón V, Czesla M, Reichelt J, Fehlert J, Hammel A, Rosendahl A et al. Ubiquitin C-Terminal Hydrolase L1 is required for regulated protein degradation through the ubiquitin proteasome system in kidney. KIDNEY INT. 2018 Jan;93(1):110-127. https://doi.org/10.1016/j.kint.2017.05.016

Bibtex

@article{3e366ff1c2fa4cc1bcb29bd08dad0aba,

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

abstract = "Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a major deubiquitinating enzyme of the nervous system and associated with the development of neurodegenerative diseases. We have previously shown that UCH-L1 is found in tubular and parietal cells of the kidney and is expressed de novo in injured podocytes. Since the role of UCH-L1 in the kidney is unknown we generated mice with a constitutive UCH-L1-deficiency to determine its role in renal health and disease. UCH-L1-deficient mice developed proteinuria, without gross changes in glomerular morphology. Tubular cells, endothelial cells, and podocytes showed signs of stress with an accumulation of oxidative-modified and polyubiquitinated proteins. Mechanistically, abnormal protein accumulation resulted from an altered proteasome abundance leading to decreased proteasomal activity, a finding exaggerated after induction of anti-podocyte nephritis. UCH-L1-deficient mice exhibited an exacerbated course of disease with increased tubulointerstitial and glomerular damage, acute renal failure, and death, the latter most likely a result of general neurologic impairment. Thus, UCH-L1 is required for regulated protein degradation in the kidney by controlling proteasome abundance. Altered proteasome abundance renders renal cells, particularly podocytes and endothelial cells, susceptible to injury.",

keywords = "Animals, Cells, Cultured, Disease Models, Animal, Glomerulonephritis, Hypotension, Immune Complex Diseases, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Mice, Knockout, Oxidation-Reduction, Podocytes, Proteasome Endopeptidase Complex, Proteinuria, Proteolysis, Ubiquitin, Ubiquitin Thiolesterase, Ubiquitination, Journal Article, Research Support, Non-U.S. Gov't",

author = "Victoria Rad{\'o}n and Maire Czesla and Julia Reichelt and Julia Fehlert and Anna Hammel and Alva Rosendahl and Jan-Hendrik Knop and Thorsten Wiech and Wenzel, {Ulrich O} and Marlies Sachs and Reinicke, {Anna T} and Stahl, {Rolf A K} and Catherine Meyer-Schwesinger",

year = "2018",

month = jan,

doi = "10.1016/j.kint.2017.05.016",

language = "English",

volume = "93",

pages = "110--127",

journal = "KIDNEY INT",

issn = "0085-2538",

publisher = "NATURE PUBLISHING GROUP",

number = "1",

}

RIS

TY - JOUR

T1 - Ubiquitin C-Terminal Hydrolase L1 is required for regulated protein degradation through the ubiquitin proteasome system in kidney

AU - Radón, Victoria

AU - Czesla, Maire

AU - Reichelt, Julia

AU - Fehlert, Julia

AU - Hammel, Anna

AU - Rosendahl, Alva

AU - Knop, Jan-Hendrik

AU - Wiech, Thorsten

AU - Wenzel, Ulrich O

AU - Sachs, Marlies

AU - Reinicke, Anna T

AU - Stahl, Rolf A K

AU - Meyer-Schwesinger, Catherine

PY - 2018/1

Y1 - 2018/1

N2 - Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a major deubiquitinating enzyme of the nervous system and associated with the development of neurodegenerative diseases. We have previously shown that UCH-L1 is found in tubular and parietal cells of the kidney and is expressed de novo in injured podocytes. Since the role of UCH-L1 in the kidney is unknown we generated mice with a constitutive UCH-L1-deficiency to determine its role in renal health and disease. UCH-L1-deficient mice developed proteinuria, without gross changes in glomerular morphology. Tubular cells, endothelial cells, and podocytes showed signs of stress with an accumulation of oxidative-modified and polyubiquitinated proteins. Mechanistically, abnormal protein accumulation resulted from an altered proteasome abundance leading to decreased proteasomal activity, a finding exaggerated after induction of anti-podocyte nephritis. UCH-L1-deficient mice exhibited an exacerbated course of disease with increased tubulointerstitial and glomerular damage, acute renal failure, and death, the latter most likely a result of general neurologic impairment. Thus, UCH-L1 is required for regulated protein degradation in the kidney by controlling proteasome abundance. Altered proteasome abundance renders renal cells, particularly podocytes and endothelial cells, susceptible to injury.

AB - Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a major deubiquitinating enzyme of the nervous system and associated with the development of neurodegenerative diseases. We have previously shown that UCH-L1 is found in tubular and parietal cells of the kidney and is expressed de novo in injured podocytes. Since the role of UCH-L1 in the kidney is unknown we generated mice with a constitutive UCH-L1-deficiency to determine its role in renal health and disease. UCH-L1-deficient mice developed proteinuria, without gross changes in glomerular morphology. Tubular cells, endothelial cells, and podocytes showed signs of stress with an accumulation of oxidative-modified and polyubiquitinated proteins. Mechanistically, abnormal protein accumulation resulted from an altered proteasome abundance leading to decreased proteasomal activity, a finding exaggerated after induction of anti-podocyte nephritis. UCH-L1-deficient mice exhibited an exacerbated course of disease with increased tubulointerstitial and glomerular damage, acute renal failure, and death, the latter most likely a result of general neurologic impairment. Thus, UCH-L1 is required for regulated protein degradation in the kidney by controlling proteasome abundance. Altered proteasome abundance renders renal cells, particularly podocytes and endothelial cells, susceptible to injury.

KW - Animals

KW - Cells, Cultured

KW - Disease Models, Animal

KW - Glomerulonephritis

KW - Hypotension

KW - Immune Complex Diseases

KW - Intracellular Signaling Peptides and Proteins

KW - Membrane Proteins

KW - Mice, Knockout

KW - Oxidation-Reduction

KW - Podocytes

KW - Proteasome Endopeptidase Complex

KW - Proteinuria

KW - Proteolysis

KW - Ubiquitin

KW - Ubiquitin Thiolesterase

KW - Ubiquitination

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.kint.2017.05.016

DO - 10.1016/j.kint.2017.05.016

M3 - SCORING: Journal article

C2 - 28754552

VL - 93

SP - 110

EP - 127

JO - KIDNEY INT

JF - KIDNEY INT

SN - 0085-2538

IS - 1

ER -