Raf kinases in signal transduction and interaction with translation machinery
In recent years, a large amount of evidence has given a central role to translational control in diseases such as cancer, tissue hypertrophy and neurodegeneration. Its deregulation can directly modulate cell cycling, transformation and survival response. The aim of this review is to describe the int...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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De Gruyter
2013-08-01
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| Series: | Biomolecular Concepts |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/bmc-2013-0003 |
| _version_ | 1818689134924922880 |
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| author | Migliaccio Nunzia Sanges Carmen Ruggiero Immacolata Martucci Nicola M. Rippa Emilia Arcari Paolo Lamberti Annalisa |
| author_facet | Migliaccio Nunzia Sanges Carmen Ruggiero Immacolata Martucci Nicola M. Rippa Emilia Arcari Paolo Lamberti Annalisa |
| author_sort | Migliaccio Nunzia |
| collection | DOAJ |
| description | In recent years, a large amount of evidence has given a central role to translational control in diseases such as cancer, tissue hypertrophy and neurodegeneration. Its deregulation can directly modulate cell cycling, transformation and survival response. The aim of this review is to describe the interaction between Raf activation and the main characters of the translational machinery, such as the elongation factor 1A (eEF1A), which has been recognized in recent years as one of the most interesting putative oncogenes. A particular emphasis is given to an intriguing non-canonical role that eEF1A can play in the relationship between the Ras→Raf-1→MEK1→ERK-1/2 and PI3K→Akt signaling pathways. Recently, our group has described a C-Raf kinase-mediated phosphorylation of eEF1A triggered by a survival pathway induced upon interferon alpha (IFNα) treatment in the human epidermoid cancer cell line (H1355). This phosphorylation seems to be the center of the survival pathway that counteracts the well-known pro-apoptotic function of IFNα. Furthermore, we have identified two new phosphorylation sites on eEF1A (Ser21 and Thr88) that are substrates for Raf kinases in vitro and, likely, in vivo as well. These residues seem to have a significant functional role in the control of cellular processes, such as cell proliferation and survival. In fact, overexpression of eEF1A2 in gemcitabine-treated cancer cells caused the upregulation of phosphoAkt and an increase in cell viability, thereby suggesting that eEF1A2 could exert its oncogenic behavior by participating in the regulation of PI3K pathway. |
| first_indexed | 2024-12-17T12:05:17Z |
| format | Article |
| id | doaj.art-fbaa661847194e27803bde6c7203b91c |
| institution | Directory Open Access Journal |
| issn | 1868-5021 1868-503X |
| language | English |
| last_indexed | 2024-12-17T12:05:17Z |
| publishDate | 2013-08-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Biomolecular Concepts |
| spelling | doaj.art-fbaa661847194e27803bde6c7203b91c2022-12-21T21:49:39ZengDe GruyterBiomolecular Concepts1868-50211868-503X2013-08-014439139910.1515/bmc-2013-0003Raf kinases in signal transduction and interaction with translation machineryMigliaccio Nunzia0Sanges Carmen1Ruggiero Immacolata2Martucci Nicola M.3Rippa Emilia4Arcari PaoloLamberti Annalisa5Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, ItalyIn recent years, a large amount of evidence has given a central role to translational control in diseases such as cancer, tissue hypertrophy and neurodegeneration. Its deregulation can directly modulate cell cycling, transformation and survival response. The aim of this review is to describe the interaction between Raf activation and the main characters of the translational machinery, such as the elongation factor 1A (eEF1A), which has been recognized in recent years as one of the most interesting putative oncogenes. A particular emphasis is given to an intriguing non-canonical role that eEF1A can play in the relationship between the Ras→Raf-1→MEK1→ERK-1/2 and PI3K→Akt signaling pathways. Recently, our group has described a C-Raf kinase-mediated phosphorylation of eEF1A triggered by a survival pathway induced upon interferon alpha (IFNα) treatment in the human epidermoid cancer cell line (H1355). This phosphorylation seems to be the center of the survival pathway that counteracts the well-known pro-apoptotic function of IFNα. Furthermore, we have identified two new phosphorylation sites on eEF1A (Ser21 and Thr88) that are substrates for Raf kinases in vitro and, likely, in vivo as well. These residues seem to have a significant functional role in the control of cellular processes, such as cell proliferation and survival. In fact, overexpression of eEF1A2 in gemcitabine-treated cancer cells caused the upregulation of phosphoAkt and an increase in cell viability, thereby suggesting that eEF1A2 could exert its oncogenic behavior by participating in the regulation of PI3K pathway.https://doi.org/10.1515/bmc-2013-0003cell proliferationraf kinasessignal transductiontranslation elongation factors |
| spellingShingle | Migliaccio Nunzia Sanges Carmen Ruggiero Immacolata Martucci Nicola M. Rippa Emilia Arcari Paolo Lamberti Annalisa Raf kinases in signal transduction and interaction with translation machinery Biomolecular Concepts cell proliferation raf kinases signal transduction translation elongation factors |
| title | Raf kinases in signal transduction and interaction with translation machinery |
| title_full | Raf kinases in signal transduction and interaction with translation machinery |
| title_fullStr | Raf kinases in signal transduction and interaction with translation machinery |
| title_full_unstemmed | Raf kinases in signal transduction and interaction with translation machinery |
| title_short | Raf kinases in signal transduction and interaction with translation machinery |
| title_sort | raf kinases in signal transduction and interaction with translation machinery |
| topic | cell proliferation raf kinases signal transduction translation elongation factors |
| url | https://doi.org/10.1515/bmc-2013-0003 |
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