Lineage-specific functions of the cytoplasmic polyadenylation regulator CPEB4 in melanoma

• Autores: Eva Pérez Guijarro
• Directores de la Tesis: María Soledad Soengas González (dir. tes.)
• Lectura: En la Universidad Autónoma de Madrid ( España ) en 2015
• Idioma: inglés
• Tribunal Calificador de la Tesis: Raúl Méndez de la Iglesia (presid.), Marcos Malumbres (secret.), Juan Ángel Recio Conde (voc.), José Luis Rodríguez Peralto (voc.), Juan Valcárcel Juárez (voc.)
• Materias:
  • Química
    • Bioquímica
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• Resumen

  • Melanoma is an increasingly frequent solid tumor that accounts for the majority of skin cancer-related deaths. Melanoma develoment is long-known for being associated sith massive altered in the transcriptome. While many of these alterations affect signaling cascades altered in other tumor types, oncogenic drivers have also been identified to be selectively restricted to melanoma. Whether these "cancer-common" and lineage-specific alterations result from the sum of individual events targeting discrete transciption factors, and/or from the action of pleiotropic RNA modulators is still unclear. Mining databases for novel tumor-associated factors, we identified a particularly intriguing upregulation of transcripts coding for Cytoplasmic Polyadenylation Binding Proteins (CPEBs) in melanoma specimens. We considerec CPEBs interesting for functional analyses as cytoplasmic mRNA poliadenylation and deadenylation can have a direct impact on mRNA half life, intracellular distribution and ultimately, time- and context-dependent traslational control. Moreover, CPEBs have not been addressed in melanoma, so we expected to provide new insights on gene regulation in this disease. Moreover, the expression and role od CPEBs in other tumor types is controversial, and therefore, our studies could also be old relevance to other malignancies. Of CPEB protein family (4 members), we selected CPEB4 for being one of ther least characterized.

    Ther main goal of this was to dissect ther contribution of CPEB4 to melanoma, which was puesued by the following specific aims.

    1. To analyze CPEB4 expression in normal skin, benign nevi and malignant melanoma.

    2. To determine whether CPEB4 ats in a lineage-specific manner in melanoma cells and7or shares functions with other normal and tumoral cell types.

    3. To dissect downstream effectors of CPEB4.