Regulation of Ras Signaling by S-Nitrosylation
Ras are a family of small GTPases that function as signal transduction mediators and are involved in cell proliferation, migration, differentiation and survival. The significance of Ras is further evidenced by the fact that Ras genes are among the most mutated oncogenes in different types of cancers...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/8/1562 |
| _version_ | 1797585666676097024 |
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| author | Sónia Simão Rafaela Ribeiro Agostinho Antonio Martínez-Ruiz Inês Maria Araújo |
| author_facet | Sónia Simão Rafaela Ribeiro Agostinho Antonio Martínez-Ruiz Inês Maria Araújo |
| author_sort | Sónia Simão |
| collection | DOAJ |
| description | Ras are a family of small GTPases that function as signal transduction mediators and are involved in cell proliferation, migration, differentiation and survival. The significance of Ras is further evidenced by the fact that Ras genes are among the most mutated oncogenes in different types of cancers. After translation, Ras proteins can be targets of post-translational modifications (PTM), which can alter the intracellular dynamics of the protein. In this review, we will focus on how S-nitrosylation of Ras affects the way these proteins interact with membranes, its cellular localization, and its activity. S-Nitrosylation occurs when a nitrosyl moiety of nitric oxide (NO) is covalently attached to a thiol group of a cysteine residue in a target protein. In Ras, the conserved Cys118 is the most surface-exposed Cys and the preferable residue for NO action, leading to the initiation of transduction events. Ras transduces the mitogen-activated protein kinases (MAPK), the phosphoinositide-3 kinase (PI3K) and the RalGEF cellular pathways. S-Nitrosylation of elements of the RalGEF cascade remains to be identified. On the contrary, it is well established that several components of the MAPK and PI3K pathways, as well as different proteins associated with these cascades, can be modified by S-nitrosylation. Overall, this review presents a better understanding of Ras S-nitrosylation, increasing the knowledge on the dynamics of these proteins in the presence of NO and the underlying implications in cellular signaling. |
| first_indexed | 2024-03-11T00:10:19Z |
| format | Article |
| id | doaj.art-3062b55b82044193bddfdd4d08666bf4 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T00:10:19Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-3062b55b82044193bddfdd4d08666bf42023-11-19T00:01:52ZengMDPI AGAntioxidants2076-39212023-08-01128156210.3390/antiox12081562Regulation of Ras Signaling by S-NitrosylationSónia Simão0Rafaela Ribeiro Agostinho1Antonio Martínez-Ruiz2Inês Maria Araújo3Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, 8005-139 Faro, PortugalAlgarve Biomedical Center Research Institute (ABC-RI), University of Algarve, 8005-139 Faro, PortugalUnidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria Princesa, 28009 Madrid, SpainAlgarve Biomedical Center Research Institute (ABC-RI), University of Algarve, 8005-139 Faro, PortugalRas are a family of small GTPases that function as signal transduction mediators and are involved in cell proliferation, migration, differentiation and survival. The significance of Ras is further evidenced by the fact that Ras genes are among the most mutated oncogenes in different types of cancers. After translation, Ras proteins can be targets of post-translational modifications (PTM), which can alter the intracellular dynamics of the protein. In this review, we will focus on how S-nitrosylation of Ras affects the way these proteins interact with membranes, its cellular localization, and its activity. S-Nitrosylation occurs when a nitrosyl moiety of nitric oxide (NO) is covalently attached to a thiol group of a cysteine residue in a target protein. In Ras, the conserved Cys118 is the most surface-exposed Cys and the preferable residue for NO action, leading to the initiation of transduction events. Ras transduces the mitogen-activated protein kinases (MAPK), the phosphoinositide-3 kinase (PI3K) and the RalGEF cellular pathways. S-Nitrosylation of elements of the RalGEF cascade remains to be identified. On the contrary, it is well established that several components of the MAPK and PI3K pathways, as well as different proteins associated with these cascades, can be modified by S-nitrosylation. Overall, this review presents a better understanding of Ras S-nitrosylation, increasing the knowledge on the dynamics of these proteins in the presence of NO and the underlying implications in cellular signaling.https://www.mdpi.com/2076-3921/12/8/1562Rasnitric oxideS-nitrosylationpost-translational modificationsneuronal cells |
| spellingShingle | Sónia Simão Rafaela Ribeiro Agostinho Antonio Martínez-Ruiz Inês Maria Araújo Regulation of Ras Signaling by S-Nitrosylation Antioxidants Ras nitric oxide S-nitrosylation post-translational modifications neuronal cells |
| title | Regulation of Ras Signaling by S-Nitrosylation |
| title_full | Regulation of Ras Signaling by S-Nitrosylation |
| title_fullStr | Regulation of Ras Signaling by S-Nitrosylation |
| title_full_unstemmed | Regulation of Ras Signaling by S-Nitrosylation |
| title_short | Regulation of Ras Signaling by S-Nitrosylation |
| title_sort | regulation of ras signaling by s nitrosylation |
| topic | Ras nitric oxide S-nitrosylation post-translational modifications neuronal cells |
| url | https://www.mdpi.com/2076-3921/12/8/1562 |
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