The role of polycomb group protein EZH2 in dendritic cell function.
Positively charged lysine residue is subjected to a plethora of post-translational modifications. Lysine methylation, while mostly studied on histone, was shown to play an exquisite role in the regulation of many cellular processes. Alone, or in combination with other post-translational modification...
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| Format: | Thesis |
| Language: | English |
| Published: |
2012
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| Online Access: | http://hdl.handle.net/10356/50950 |
| _version_ | 1811677632810450944 |
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| author | Gunawan, Merry. |
| author2 | Su I-Hsin |
| author_facet | Su I-Hsin Gunawan, Merry. |
| author_sort | Gunawan, Merry. |
| collection | NTU |
| description | Positively charged lysine residue is subjected to a plethora of post-translational modifications. Lysine methylation, while mostly studied on histone, was shown to play an exquisite role in the regulation of many cellular processes. Alone, or in combination with other post-translational modifications, lysine methylation was shown to critically alter the function, interaction properties and stability of its substrates. Lysine methyltransferase Ezh2 was found in the nucleus where it exerts its epigenetic silencing function through histone methylation, and in the cytosol where it plays an unexpected role in cytoskeletal rearrangements.
In this report, we present evidence showing that Ezh2 regulates integrin signaling activity, which is critical for Dendritic Cell’s (DC’s) motility and recruitment. We observed that Ezh2 deficiency caused severe reduction of DC motility, and accordingly, Ezh2-deficient DCs formed long-lived focal adhesion complexes which are commonly found in slow migrating cells such as fibroblast and epithelial cells. Examination of integrin signaling which regulates focal adhesion formation and cell migration properties revealed that Ezh2 plays a critical role in integrin signaling, as shown by hyper-phosphorylation of Focal Adhesion Kinase (FAK), increased cell adhesion, and exaggerated cell spreading in Ezh2-deficient DCs. At the molecular level, we found that Ezh2 is associated together with Vav and Talin, and that Ezh2 were able to methylate Talin, as shown by in vitro methyl-transferase assay. Consequently, integrin-dependent transendothelial migration of Ezh2-deficient DCs is impaired, as seen in the attenuated induction of EAE, an animal model for multiple sclerosis. Our results demonstrate for the first time, that adhesion dynamic is regulated through lysine methylation |
| first_indexed | 2024-10-01T02:40:28Z |
| format | Thesis |
| id | ntu-10356/50950 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:40:28Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | ntu-10356/509502023-02-28T18:32:07Z The role of polycomb group protein EZH2 in dendritic cell function. Gunawan, Merry. Su I-Hsin School of Biological Sciences DRNTU::Science::Biological sciences::Molecular biology Positively charged lysine residue is subjected to a plethora of post-translational modifications. Lysine methylation, while mostly studied on histone, was shown to play an exquisite role in the regulation of many cellular processes. Alone, or in combination with other post-translational modifications, lysine methylation was shown to critically alter the function, interaction properties and stability of its substrates. Lysine methyltransferase Ezh2 was found in the nucleus where it exerts its epigenetic silencing function through histone methylation, and in the cytosol where it plays an unexpected role in cytoskeletal rearrangements. In this report, we present evidence showing that Ezh2 regulates integrin signaling activity, which is critical for Dendritic Cell’s (DC’s) motility and recruitment. We observed that Ezh2 deficiency caused severe reduction of DC motility, and accordingly, Ezh2-deficient DCs formed long-lived focal adhesion complexes which are commonly found in slow migrating cells such as fibroblast and epithelial cells. Examination of integrin signaling which regulates focal adhesion formation and cell migration properties revealed that Ezh2 plays a critical role in integrin signaling, as shown by hyper-phosphorylation of Focal Adhesion Kinase (FAK), increased cell adhesion, and exaggerated cell spreading in Ezh2-deficient DCs. At the molecular level, we found that Ezh2 is associated together with Vav and Talin, and that Ezh2 were able to methylate Talin, as shown by in vitro methyl-transferase assay. Consequently, integrin-dependent transendothelial migration of Ezh2-deficient DCs is impaired, as seen in the attenuated induction of EAE, an animal model for multiple sclerosis. Our results demonstrate for the first time, that adhesion dynamic is regulated through lysine methylation Doctor of Philosophy (SBS) 2012-12-24T04:20:58Z 2012-12-24T04:20:58Z 2012 2012 Thesis http://hdl.handle.net/10356/50950 en 130 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences::Molecular biology Gunawan, Merry. The role of polycomb group protein EZH2 in dendritic cell function. |
| title | The role of polycomb group protein EZH2 in dendritic cell function. |
| title_full | The role of polycomb group protein EZH2 in dendritic cell function. |
| title_fullStr | The role of polycomb group protein EZH2 in dendritic cell function. |
| title_full_unstemmed | The role of polycomb group protein EZH2 in dendritic cell function. |
| title_short | The role of polycomb group protein EZH2 in dendritic cell function. |
| title_sort | role of polycomb group protein ezh2 in dendritic cell function |
| topic | DRNTU::Science::Biological sciences::Molecular biology |
| url | http://hdl.handle.net/10356/50950 |
| work_keys_str_mv | AT gunawanmerry theroleofpolycombgroupproteinezh2indendriticcellfunction AT gunawanmerry roleofpolycombgroupproteinezh2indendriticcellfunction |