The role of the RPL5/RPL11/5S rRNA complex in mediating p53 levels in response to c-Myc depletion in colorectal carcinoma

Autor/a

Morcelle Magaña, Carmen

Director/a

Thomas, George

Tutor/a

Tauler Girona, Albert

Fecha de defensa

2017-09-19

Páginas

159 p.



Departamento/Instituto

Universitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació

Resumen

In most human cancers, the c-Myc transcription factor is deregulated and/or its levels are elevated, particularly in colorectal cancer (CRC). Earlier studies suggested a direct relationship between ribosome biogenesis and c-Myc-induced tumorigenesis, with recent reports arguing that ribosomal proteins L5 (RPL5) and RPL11 act against c- Myc-driven tumorigenesis as tumor suppressors by inhibiting MDM2 and inducing p53 stabilization. Our laboratory recently showed that upon inhibition of ribosome biogenesis, a nascent pre-ribosomal complex containing RPL5, RPL11 and 5S rRNA is redirected from 60S ribosome biogenesis to the inhibition of MDM2 and p53 stabilization. We have termed this response the impaired ribosome biogenesis checkpoint (IRBC). Here, we demonstrate that c-Myc silencing causes a drop in p53 protein levels through increased proteasome degradation. Moreover, c-Myc depletion significantly reduces the levels of the RPL5/RPL11/5S rRNA complex, even following impaired ribosome biogenesis by treatment with Actinomycin D, a RNA polymerase I inhibitor. Thus, diminished p53 stability appears to be mediated by a reduction of the RPL5/RPL11/5S rRNA complex and a decrease of the inhibition of MDM2. This thesis examines the relationship between c-Myc, p53 and components of the IRBC complex, including the 5S rRNA, defining a mechanism by which cells respond to c-Myc levels.

Palabras clave

Oncologia; Oncología; Oncology; Marcadors tumorals; Marcadores tumorales; Tumor markers; Ribosomes; Ribosomas

Materias

616 - Patología. Medicina clínica. Oncología

Área de conocimiento

Ciències de la Salut

Documentos

CMM_PhD_THESIS.pdf

22.27Mb

 

Derechos

L'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc-nd/4.0/
L'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc-nd/4.0/

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