Tesis doctoral de Erik Wolfgang Oliemuller García
Collapsin response mediator protein 2 (crmp-2) is a tubulin adaptor protein firstly described in neurons. This protein participates in tubulin polymerization by adding tubulin dimers to the growing tip of microtubules. Crmp-2 function as tubulin adaptor and is regulated by its phosphorylation in such a way that it decreases its affinity for tubulin and abrogates microtubule polymerization. microtubules are involved in a wide variety of cellular functions being most relevant its participation in cell division and migration; both processes being deregulated in cancer. There is scarce data on crmp-2 expression and phosphorylation in cancer. In this work we have described that crmp-2 is over-expressed in immortalized and transformed lung epithelial cells when compared to normal epithelium. Crmp-2 phosphorylation in ser 518 seems to be exclusive of transformed nsclc cells. in vitro experiments were performed by over-expressing crmp-2 and its phosphomimetic and phosphodefective mutants in a549 nsclc cells. After performing cell adhesion, migration and clonogenecity assays, crmp-2 phosphomimetic clones offered a more agressive behaviour. In vivo experiments performed in xenographt models in nude mice rendered contradictory results: cells expressing the phosphomimetic form of crmp-2 produced the smallest tumors while those expressing crmp-2 phosohodefective mutants resulted in the greatest but more apoptotic-prone ones. the study of the participation of crmp-2 in mitosis revealed its interaction with tubulin spindle during mitosis in a phosphorylation dependent way. Changes in crmp-2 phosphorylation status lead to alterations in the duration of several mitotic phases and aberrant cytocinesis, in the case of cells expressing crmp-2 phosphomimetic mutants. crmp-2 phosphorylation gsk-3β mitosis nsclc microtubules
Datos académicos de la tesis doctoral «Estudio de la función de la proteína mediadora de respuesta a colapsinas 2 (crmp-2) en cáncer de pulmón no microcítico«
- Título de la tesis: Estudio de la función de la proteína mediadora de respuesta a colapsinas 2 (crmp-2) en cáncer de pulmón no microcítico
- Autor: Erik Wolfgang Oliemuller García
- Universidad: Navarra
- Fecha de lectura de la tesis: 27/05/2011
Dirección y tribunal
- Director de la tesis
- Ana Rouzaut Subira
- Tribunal
- Presidente del tribunal: María pilar Sesma egozcue
- susana Llanos girón (vocal)
- ricardo Madrid gonzalez (vocal)
- Carlos gabriel de Miguel vazquez (vocal)