Identification and functional analysis of SOX10 phosphorylation sites in melanoma.
The transcription factor SOX10 plays an important role in vertebrate neural crest development, including the establishment and maintenance of the melanocyte lineage. SOX10 is also highly expressed in melanoma tumors, and SOX10 expression increases with tumor progression. The suppression of SOX10 in...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5760019?pdf=render |
| _version_ | 1818294118666731520 |
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| author | Julia C Cronin Stacie K Loftus Laura L Baxter Steve Swatkoski Marjan Gucek William J Pavan |
| author_facet | Julia C Cronin Stacie K Loftus Laura L Baxter Steve Swatkoski Marjan Gucek William J Pavan |
| author_sort | Julia C Cronin |
| collection | DOAJ |
| description | The transcription factor SOX10 plays an important role in vertebrate neural crest development, including the establishment and maintenance of the melanocyte lineage. SOX10 is also highly expressed in melanoma tumors, and SOX10 expression increases with tumor progression. The suppression of SOX10 in melanoma cells activates TGF-β signaling and can promote resistance to BRAF and MEK inhibitors. Since resistance to BRAF/MEK inhibitors is seen in the majority of melanoma patients, there is an immediate need to assess the underlying biology that mediates resistance and to identify new targets for combinatorial therapeutic approaches. Previously, we demonstrated that SOX10 protein is required for tumor initiation, maintenance and survival. Here, we present data that support phosphorylation as a mechanism employed by melanoma cells to tightly regulate SOX10 expression. Mass spectrometry identified eight phosphorylation sites contained within SOX10, three of which (S24, S45 and T240) were selected for further analysis based on their location within predicted MAPK/CDK binding motifs. SOX10 mutations were generated at these phosphorylation sites to assess their impact on SOX10 protein function in melanoma cells, including transcriptional activation on target promoters, subcellular localization, and stability. These data further our understanding of SOX10 protein regulation and provide critical information for identification of molecular pathways that modulate SOX10 protein levels in melanoma, with the ultimate goal of discovering novel targets for more effective combinatorial therapeutic approaches for melanoma patients. |
| first_indexed | 2024-12-13T03:26:40Z |
| format | Article |
| id | doaj.art-a7194cd509194d4ab39819d3197c3f97 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T03:26:40Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a7194cd509194d4ab39819d3197c3f972022-12-22T00:01:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01131e019083410.1371/journal.pone.0190834Identification and functional analysis of SOX10 phosphorylation sites in melanoma.Julia C CroninStacie K LoftusLaura L BaxterSteve SwatkoskiMarjan GucekWilliam J PavanThe transcription factor SOX10 plays an important role in vertebrate neural crest development, including the establishment and maintenance of the melanocyte lineage. SOX10 is also highly expressed in melanoma tumors, and SOX10 expression increases with tumor progression. The suppression of SOX10 in melanoma cells activates TGF-β signaling and can promote resistance to BRAF and MEK inhibitors. Since resistance to BRAF/MEK inhibitors is seen in the majority of melanoma patients, there is an immediate need to assess the underlying biology that mediates resistance and to identify new targets for combinatorial therapeutic approaches. Previously, we demonstrated that SOX10 protein is required for tumor initiation, maintenance and survival. Here, we present data that support phosphorylation as a mechanism employed by melanoma cells to tightly regulate SOX10 expression. Mass spectrometry identified eight phosphorylation sites contained within SOX10, three of which (S24, S45 and T240) were selected for further analysis based on their location within predicted MAPK/CDK binding motifs. SOX10 mutations were generated at these phosphorylation sites to assess their impact on SOX10 protein function in melanoma cells, including transcriptional activation on target promoters, subcellular localization, and stability. These data further our understanding of SOX10 protein regulation and provide critical information for identification of molecular pathways that modulate SOX10 protein levels in melanoma, with the ultimate goal of discovering novel targets for more effective combinatorial therapeutic approaches for melanoma patients.http://europepmc.org/articles/PMC5760019?pdf=render |
| spellingShingle | Julia C Cronin Stacie K Loftus Laura L Baxter Steve Swatkoski Marjan Gucek William J Pavan Identification and functional analysis of SOX10 phosphorylation sites in melanoma. PLoS ONE |
| title | Identification and functional analysis of SOX10 phosphorylation sites in melanoma. |
| title_full | Identification and functional analysis of SOX10 phosphorylation sites in melanoma. |
| title_fullStr | Identification and functional analysis of SOX10 phosphorylation sites in melanoma. |
| title_full_unstemmed | Identification and functional analysis of SOX10 phosphorylation sites in melanoma. |
| title_short | Identification and functional analysis of SOX10 phosphorylation sites in melanoma. |
| title_sort | identification and functional analysis of sox10 phosphorylation sites in melanoma |
| url | http://europepmc.org/articles/PMC5760019?pdf=render |
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