CSDE1 isoforms in cancer progression and suppression
The RNA-binding protein CSDE1 is a key regulator of mRNA stability and translation, involved in a wide range of biological processes. Alterations of CSDE1 expression and/or genetic mutations have been found in neurodevelopmental disorders and in several human tumors, where CSDE1 displays context-spe...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/691918 |
| Acceso en línea: | http://hdl.handle.net/10803/691918 |
| Access Level: | acceso embargado |
| Palabra clave: | Cancer RNA-Binding proteins Translational regulation CSDE1 Isoforms Cáncer Proteína de unión a ARN Regulación de la traducción Isoformas 577 |
| Sumario: | The RNA-binding protein CSDE1 is a key regulator of mRNA stability and translation, involved in a wide range of biological processes. Alterations of CSDE1 expression and/or genetic mutations have been found in neurodevelopmental disorders and in several human tumors, where CSDE1 displays context-specific roles. We have previously shown that CSDE1 functions as an oncoprotein in melanoma, where it promotes invasion and metastasis, whereas it behaves as a tumour suppressor in squamous cell carcinoma by promoting oncogene-induced senescence (1, 2). The reasons underlying these context-specific behaviours are so far unknown. To unveil whether different CSDE1 “proteoforms”, are a possible explanation for this context-specificity, we have combined Nanopore sequencing with one and two-dimensional gel analysis to characterize CSDE1 in melanoma cells and in keratinocytes. We have defined tissue-specific proteins, including one major isoform expressed in melanoma patient samples regardless of tumor stage, whose levels increase dramatically upon cell transformation. Notably, we have also detected differential CSDE1 PTMs and subcellular localization correlating with cell malignancy. Our data is consistent with a model where PTMs of CSDE1 are central to direct its function to shape the malignant phenotypes. (1) Wurth et al., Cancer Cell (2016). PMID: 27908735 (2) Avolio et al., Cell Reports (2022). PMID: 35021076 |
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