O-GlcNAcylation: a new cancer hallmark?
O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification consisting in the addition of a sugar moiety to serine/threonine residues of cytosolic or nuclear proteins. Catalyzed by OGT and removed by OGA, this dynamic modification is dependent on environmenta...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-08-01
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| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fendo.2013.00099/full |
| _version_ | 1818929679886712832 |
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| author | Yann eFardini Vanessa eDehennaut Tony eLefebvre Tarik eISSAD |
| author_facet | Yann eFardini Vanessa eDehennaut Tony eLefebvre Tarik eISSAD |
| author_sort | Yann eFardini |
| collection | DOAJ |
| description | O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification consisting in the addition of a sugar moiety to serine/threonine residues of cytosolic or nuclear proteins. Catalyzed by OGT and removed by OGA, this dynamic modification is dependent on environmental glucose concentration. O-GlcNAcylation regulates the activities of a wide panel of proteins involved in almost all aspects of cell biology. As a nutrient sensor, O-GlcNAcylation can relay the effects of excessive nutritional intake, an important cancer risk factor, on protein activities and cellular functions. Indeed, O-GlcNAcylation has been shown to play a significant role in cancer development through different mechanisms. O-GlcNAcylation and OGT levels are increased in different cancers (breast, prostate, colon...) and vary during cell cycle progression. Modulating their expression or activity can alter cancer cell proliferation and/or invasion. Interestingly, major oncogenic factors have been shown to be directly O-GlcNAcylated (p53, MYC, NFκB, β-catenin...). Furthermore, chromatin dynamics is modulated by O-GlcNAc. DNA methylation enzymes of the Tet family, involved epigenetic alterations associated with cancer, were recently found to interact with and target OGT to multi-molecular chromatin remodelling complexes. Consistently, histones are subjected to O-GlcNAc modifications which regulate their function. Increasing number of evidences point out the central involvement of O-GlcNAcylation in tumorigenesis, justifying the attention received as a potential new approach for cancer treatment. However, comprehension of the underlying mechanism remains at its beginnings. Future challenge will be to address directly the role of O-GlcNAc-modified residues in oncogenic-related proteins to eventually propose novel strategies to alter cancer development and/or progression. |
| first_indexed | 2024-12-20T03:48:39Z |
| format | Article |
| id | doaj.art-8f6da5bc2c9444e8bbd6940224d913d3 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-20T03:48:39Z |
| publishDate | 2013-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-8f6da5bc2c9444e8bbd6940224d913d32022-12-21T19:54:32ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922013-08-01410.3389/fendo.2013.0009957913O-GlcNAcylation: a new cancer hallmark?Yann eFardini0Vanessa eDehennaut1Tony eLefebvre2Tarik eISSAD3INSERM U1016, CNRS UMR8104, University Paris DescartesCNRS UMR 8576, University of Lille 1CNRS UMR 8576, University of Lille 1INSERM U1016, CNRS UMR8104, University Paris DescartesO-linked N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification consisting in the addition of a sugar moiety to serine/threonine residues of cytosolic or nuclear proteins. Catalyzed by OGT and removed by OGA, this dynamic modification is dependent on environmental glucose concentration. O-GlcNAcylation regulates the activities of a wide panel of proteins involved in almost all aspects of cell biology. As a nutrient sensor, O-GlcNAcylation can relay the effects of excessive nutritional intake, an important cancer risk factor, on protein activities and cellular functions. Indeed, O-GlcNAcylation has been shown to play a significant role in cancer development through different mechanisms. O-GlcNAcylation and OGT levels are increased in different cancers (breast, prostate, colon...) and vary during cell cycle progression. Modulating their expression or activity can alter cancer cell proliferation and/or invasion. Interestingly, major oncogenic factors have been shown to be directly O-GlcNAcylated (p53, MYC, NFκB, β-catenin...). Furthermore, chromatin dynamics is modulated by O-GlcNAc. DNA methylation enzymes of the Tet family, involved epigenetic alterations associated with cancer, were recently found to interact with and target OGT to multi-molecular chromatin remodelling complexes. Consistently, histones are subjected to O-GlcNAc modifications which regulate their function. Increasing number of evidences point out the central involvement of O-GlcNAcylation in tumorigenesis, justifying the attention received as a potential new approach for cancer treatment. However, comprehension of the underlying mechanism remains at its beginnings. Future challenge will be to address directly the role of O-GlcNAc-modified residues in oncogenic-related proteins to eventually propose novel strategies to alter cancer development and/or progression.http://journal.frontiersin.org/Journal/10.3389/fendo.2013.00099/fullCell CycleTranscription FactorsCancerepigeneticsmetastasisoncogenesis |
| spellingShingle | Yann eFardini Vanessa eDehennaut Tony eLefebvre Tarik eISSAD O-GlcNAcylation: a new cancer hallmark? Frontiers in Endocrinology Cell Cycle Transcription Factors Cancer epigenetics metastasis oncogenesis |
| title | O-GlcNAcylation: a new cancer hallmark? |
| title_full | O-GlcNAcylation: a new cancer hallmark? |
| title_fullStr | O-GlcNAcylation: a new cancer hallmark? |
| title_full_unstemmed | O-GlcNAcylation: a new cancer hallmark? |
| title_short | O-GlcNAcylation: a new cancer hallmark? |
| title_sort | o glcnacylation a new cancer hallmark |
| topic | Cell Cycle Transcription Factors Cancer epigenetics metastasis oncogenesis |
| url | http://journal.frontiersin.org/Journal/10.3389/fendo.2013.00099/full |
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