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Phosphorylation of Nicastrin by SGK1 Leads to Its Degradation through Lysosomal and Proteasomal Pathways
The gamma-secretase complex is involved in the intramembranous proteolysis of a variety of substrates, including the amyloid precursor protein and the Notch receptor. Nicastrin (NCT) is an essential component of the gamma-secretase complex and functions as a receptor for gamma-secretase substrates....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349648/ https://www.ncbi.nlm.nih.gov/pubmed/22590650 http://dx.doi.org/10.1371/journal.pone.0037111 |
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author | Mo, Jung-Soon Yoon, Ji-Hye Hong, Ji-Ae Kim, Mi-Yeon Ann, Eun-Jung Ahn, Ji-Seon Kim, Su-Man Baek, Hyeong-Jin Lang, Florian Choi, Eui-Ju Park, Hee-Sae |
author_facet | Mo, Jung-Soon Yoon, Ji-Hye Hong, Ji-Ae Kim, Mi-Yeon Ann, Eun-Jung Ahn, Ji-Seon Kim, Su-Man Baek, Hyeong-Jin Lang, Florian Choi, Eui-Ju Park, Hee-Sae |
author_sort | Mo, Jung-Soon |
collection | PubMed |
description | The gamma-secretase complex is involved in the intramembranous proteolysis of a variety of substrates, including the amyloid precursor protein and the Notch receptor. Nicastrin (NCT) is an essential component of the gamma-secretase complex and functions as a receptor for gamma-secretase substrates. In this study, we determined that serum- and glucocorticoid-induced protein kinase 1 (SGK1) markedly reduced the protein stability of NCT. The SGK1 kinase activity was decisive for NCT degradation and endogenous SGK1 inhibited gamma-secretase activity. SGK1 downregulates NCT protein levels via proteasomal and lysosomal pathways. Furthermore, SGK1 directly bound to and phosphorylated NCT on Ser437, thereby promoting protein degradation. Collectively, our findings indicate that SGK1 is a gamma-secretase regulator presumably effective through phosphorylation and degradation of NCT. |
format | Online Article Text |
id | pubmed-3349648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33496482012-05-15 Phosphorylation of Nicastrin by SGK1 Leads to Its Degradation through Lysosomal and Proteasomal Pathways Mo, Jung-Soon Yoon, Ji-Hye Hong, Ji-Ae Kim, Mi-Yeon Ann, Eun-Jung Ahn, Ji-Seon Kim, Su-Man Baek, Hyeong-Jin Lang, Florian Choi, Eui-Ju Park, Hee-Sae PLoS One Research Article The gamma-secretase complex is involved in the intramembranous proteolysis of a variety of substrates, including the amyloid precursor protein and the Notch receptor. Nicastrin (NCT) is an essential component of the gamma-secretase complex and functions as a receptor for gamma-secretase substrates. In this study, we determined that serum- and glucocorticoid-induced protein kinase 1 (SGK1) markedly reduced the protein stability of NCT. The SGK1 kinase activity was decisive for NCT degradation and endogenous SGK1 inhibited gamma-secretase activity. SGK1 downregulates NCT protein levels via proteasomal and lysosomal pathways. Furthermore, SGK1 directly bound to and phosphorylated NCT on Ser437, thereby promoting protein degradation. Collectively, our findings indicate that SGK1 is a gamma-secretase regulator presumably effective through phosphorylation and degradation of NCT. Public Library of Science 2012-05-10 /pmc/articles/PMC3349648/ /pubmed/22590650 http://dx.doi.org/10.1371/journal.pone.0037111 Text en Mo et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mo, Jung-Soon Yoon, Ji-Hye Hong, Ji-Ae Kim, Mi-Yeon Ann, Eun-Jung Ahn, Ji-Seon Kim, Su-Man Baek, Hyeong-Jin Lang, Florian Choi, Eui-Ju Park, Hee-Sae Phosphorylation of Nicastrin by SGK1 Leads to Its Degradation through Lysosomal and Proteasomal Pathways |
title | Phosphorylation of Nicastrin by SGK1 Leads to Its Degradation through Lysosomal and Proteasomal Pathways |
title_full | Phosphorylation of Nicastrin by SGK1 Leads to Its Degradation through Lysosomal and Proteasomal Pathways |
title_fullStr | Phosphorylation of Nicastrin by SGK1 Leads to Its Degradation through Lysosomal and Proteasomal Pathways |
title_full_unstemmed | Phosphorylation of Nicastrin by SGK1 Leads to Its Degradation through Lysosomal and Proteasomal Pathways |
title_short | Phosphorylation of Nicastrin by SGK1 Leads to Its Degradation through Lysosomal and Proteasomal Pathways |
title_sort | phosphorylation of nicastrin by sgk1 leads to its degradation through lysosomal and proteasomal pathways |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349648/ https://www.ncbi.nlm.nih.gov/pubmed/22590650 http://dx.doi.org/10.1371/journal.pone.0037111 |
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