RAB7A Regulates Vimentin Phosphorylation through AKT and PAK
RAB7A is a small GTPase that controls the late endocytic pathway but also cell migration through RAC1 (Ras-related C3 botulinum toxin substrate 1) and vimentin. In fact, RAB7A regulates vimentin phosphorylation at different sites and vimentin assembly, and, in this study, we identified vimentin doma...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/9/2220 |
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| author | Roberta Romano Matteo Calcagnile Azzurra Margiotta Lorenzo Franci Mario Chiariello Pietro Alifano Cecilia Bucci |
| author_facet | Roberta Romano Matteo Calcagnile Azzurra Margiotta Lorenzo Franci Mario Chiariello Pietro Alifano Cecilia Bucci |
| author_sort | Roberta Romano |
| collection | DOAJ |
| description | RAB7A is a small GTPase that controls the late endocytic pathway but also cell migration through RAC1 (Ras-related C3 botulinum toxin substrate 1) and vimentin. In fact, RAB7A regulates vimentin phosphorylation at different sites and vimentin assembly, and, in this study, we identified vimentin domains interacting with RAB7A. As several kinases could be responsible for vimentin phosphorylation, we investigated whether modulation of RAB7A expression affects the activity of these kinases. We discovered that RAB7A regulates AKT and PAK1, and we demonstrated that increased vimentin phosphorylation at Ser38 (Serine 38), observed upon RAB7A overexpression, is due to AKT activity. As AKT and PAK1 are key regulators of several cellular events, we investigated if RAB7A could have a role in these processes by modulating AKT and PAK1 activity. We found that RAB7A protein levels affected beta-catenin and caspase 9 expression. We also observed the downregulation of cofilin-1 and decreased matrix metalloproteinase 2 (MMP2) activity upon RAB7A silencing. Altogether these results demonstrate that RAB7A regulates AKT and PAK1 kinases, affecting their downstream effectors and the processes they regulate, suggesting that RAB7A could have a role in a number of cancer hallmarks. |
| first_indexed | 2024-03-10T11:40:25Z |
| format | Article |
| id | doaj.art-6038755d25244381a6ee3c9c63e57e35 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T11:40:25Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6038755d25244381a6ee3c9c63e57e352023-11-21T18:32:03ZengMDPI AGCancers2072-66942021-05-01139222010.3390/cancers13092220RAB7A Regulates Vimentin Phosphorylation through AKT and PAKRoberta Romano0Matteo Calcagnile1Azzurra Margiotta2Lorenzo Franci3Mario Chiariello4Pietro Alifano5Cecilia Bucci6Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, 73100 Lecce, ItalyDepartment of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, 73100 Lecce, ItalyDepartment of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, 73100 Lecce, ItalyIstituto di Fisiologia Clinica (IFC), Consiglio Nazionale delle Ricerche (CNR), 53100 Siena, ItalyIstituto di Fisiologia Clinica (IFC), Consiglio Nazionale delle Ricerche (CNR), 53100 Siena, ItalyDepartment of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, 73100 Lecce, ItalyDepartment of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, 73100 Lecce, ItalyRAB7A is a small GTPase that controls the late endocytic pathway but also cell migration through RAC1 (Ras-related C3 botulinum toxin substrate 1) and vimentin. In fact, RAB7A regulates vimentin phosphorylation at different sites and vimentin assembly, and, in this study, we identified vimentin domains interacting with RAB7A. As several kinases could be responsible for vimentin phosphorylation, we investigated whether modulation of RAB7A expression affects the activity of these kinases. We discovered that RAB7A regulates AKT and PAK1, and we demonstrated that increased vimentin phosphorylation at Ser38 (Serine 38), observed upon RAB7A overexpression, is due to AKT activity. As AKT and PAK1 are key regulators of several cellular events, we investigated if RAB7A could have a role in these processes by modulating AKT and PAK1 activity. We found that RAB7A protein levels affected beta-catenin and caspase 9 expression. We also observed the downregulation of cofilin-1 and decreased matrix metalloproteinase 2 (MMP2) activity upon RAB7A silencing. Altogether these results demonstrate that RAB7A regulates AKT and PAK1 kinases, affecting their downstream effectors and the processes they regulate, suggesting that RAB7A could have a role in a number of cancer hallmarks.https://www.mdpi.com/2072-6694/13/9/2220cell migrationintermediate filamentsRAC1beta-cateninNF-kBcofilin |
| spellingShingle | Roberta Romano Matteo Calcagnile Azzurra Margiotta Lorenzo Franci Mario Chiariello Pietro Alifano Cecilia Bucci RAB7A Regulates Vimentin Phosphorylation through AKT and PAK Cancers cell migration intermediate filaments RAC1 beta-catenin NF-kB cofilin |
| title | RAB7A Regulates Vimentin Phosphorylation through AKT and PAK |
| title_full | RAB7A Regulates Vimentin Phosphorylation through AKT and PAK |
| title_fullStr | RAB7A Regulates Vimentin Phosphorylation through AKT and PAK |
| title_full_unstemmed | RAB7A Regulates Vimentin Phosphorylation through AKT and PAK |
| title_short | RAB7A Regulates Vimentin Phosphorylation through AKT and PAK |
| title_sort | rab7a regulates vimentin phosphorylation through akt and pak |
| topic | cell migration intermediate filaments RAC1 beta-catenin NF-kB cofilin |
| url | https://www.mdpi.com/2072-6694/13/9/2220 |
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