Cargando…

Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2

Glycosylation inhibition has great potential in cancer treatment. However, the corresponding cellular response, protein expression and glycosylation changes remain unclear. As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has bec...

Descripción completa

Detalles Bibliográficos
Autores principales: Cao, Xinyi, Meng, Peiyi, Shao, Yuyin, Yan, Guoquan, Yao, Jun, Zhou, Xinwen, Liu, Chao, Zhang, Lei, Shu, Hong, Lu, Haojie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9092021/
https://www.ncbi.nlm.nih.gov/pubmed/35573732
http://dx.doi.org/10.3389/fmolb.2022.899192
_version_ 1784705052375515136
author Cao, Xinyi
Meng, Peiyi
Shao, Yuyin
Yan, Guoquan
Yao, Jun
Zhou, Xinwen
Liu, Chao
Zhang, Lei
Shu, Hong
Lu, Haojie
author_facet Cao, Xinyi
Meng, Peiyi
Shao, Yuyin
Yan, Guoquan
Yao, Jun
Zhou, Xinwen
Liu, Chao
Zhang, Lei
Shu, Hong
Lu, Haojie
author_sort Cao, Xinyi
collection PubMed
description Glycosylation inhibition has great potential in cancer treatment. However, the corresponding cellular response, protein expression and glycosylation changes remain unclear. As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. Here for the first time, we applied a nascent proteomic method to investigate the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line. Besides, hydrophilic interaction liquid chromatography (HILIC) was adopted for the enrichment of glycosylated peptides. Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. Moreover, the alterations of LAMP2 site-specific intact N-glycopeptides were comprehensively assessed. NGI-1 treatment also led to the inhibition of Cathepsin D maturation and the induction of autophagy. In summary, we provided evidence that NGI-1 repressed the expression of glycosylated LAMP2 accompanied with the occurrence of lysosomal defects and autophagy.
format Online
Article
Text
id pubmed-9092021
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-90920212022-05-12 Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2 Cao, Xinyi Meng, Peiyi Shao, Yuyin Yan, Guoquan Yao, Jun Zhou, Xinwen Liu, Chao Zhang, Lei Shu, Hong Lu, Haojie Front Mol Biosci Molecular Biosciences Glycosylation inhibition has great potential in cancer treatment. However, the corresponding cellular response, protein expression and glycosylation changes remain unclear. As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. Here for the first time, we applied a nascent proteomic method to investigate the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line. Besides, hydrophilic interaction liquid chromatography (HILIC) was adopted for the enrichment of glycosylated peptides. Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. Moreover, the alterations of LAMP2 site-specific intact N-glycopeptides were comprehensively assessed. NGI-1 treatment also led to the inhibition of Cathepsin D maturation and the induction of autophagy. In summary, we provided evidence that NGI-1 repressed the expression of glycosylated LAMP2 accompanied with the occurrence of lysosomal defects and autophagy. Frontiers Media S.A. 2022-04-27 /pmc/articles/PMC9092021/ /pubmed/35573732 http://dx.doi.org/10.3389/fmolb.2022.899192 Text en Copyright © 2022 Cao, Meng, Shao, Yan, Yao, Zhou, Liu, Zhang, Shu and Lu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Cao, Xinyi
Meng, Peiyi
Shao, Yuyin
Yan, Guoquan
Yao, Jun
Zhou, Xinwen
Liu, Chao
Zhang, Lei
Shu, Hong
Lu, Haojie
Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2
title Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2
title_full Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2
title_fullStr Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2
title_full_unstemmed Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2
title_short Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2
title_sort nascent glycoproteome reveals that n-linked glycosylation inhibitor-1 suppresses expression of glycosylated lysosome-associated membrane protein-2
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9092021/
https://www.ncbi.nlm.nih.gov/pubmed/35573732
http://dx.doi.org/10.3389/fmolb.2022.899192
work_keys_str_mv AT caoxinyi nascentglycoproteomerevealsthatnlinkedglycosylationinhibitor1suppressesexpressionofglycosylatedlysosomeassociatedmembraneprotein2
AT mengpeiyi nascentglycoproteomerevealsthatnlinkedglycosylationinhibitor1suppressesexpressionofglycosylatedlysosomeassociatedmembraneprotein2
AT shaoyuyin nascentglycoproteomerevealsthatnlinkedglycosylationinhibitor1suppressesexpressionofglycosylatedlysosomeassociatedmembraneprotein2
AT yanguoquan nascentglycoproteomerevealsthatnlinkedglycosylationinhibitor1suppressesexpressionofglycosylatedlysosomeassociatedmembraneprotein2
AT yaojun nascentglycoproteomerevealsthatnlinkedglycosylationinhibitor1suppressesexpressionofglycosylatedlysosomeassociatedmembraneprotein2
AT zhouxinwen nascentglycoproteomerevealsthatnlinkedglycosylationinhibitor1suppressesexpressionofglycosylatedlysosomeassociatedmembraneprotein2
AT liuchao nascentglycoproteomerevealsthatnlinkedglycosylationinhibitor1suppressesexpressionofglycosylatedlysosomeassociatedmembraneprotein2
AT zhanglei nascentglycoproteomerevealsthatnlinkedglycosylationinhibitor1suppressesexpressionofglycosylatedlysosomeassociatedmembraneprotein2
AT shuhong nascentglycoproteomerevealsthatnlinkedglycosylationinhibitor1suppressesexpressionofglycosylatedlysosomeassociatedmembraneprotein2
AT luhaojie nascentglycoproteomerevealsthatnlinkedglycosylationinhibitor1suppressesexpressionofglycosylatedlysosomeassociatedmembraneprotein2