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Estudo dos resíduos de fosforilação da proteína pro-apoptótica BimEL em mitose

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Resumo:Proliferation and cell death are intertwined, highly regulated processes that are extremely important to the homeostasis of living organisms. The machineries of cell cycle and apoptosis, a form of programmed cell death, are known to interact in many ways. However, the proteins involved in the crosstalk between the two pathways during mitosis have only recently started to be identified and studied. One of those proteins is BimEL, a pro-apoptotic member of the Bcl-2 family of proteins. Our group has shown that in mitosis BimEL is phosphorylated and resides in mitochondria, whereas in interphase it is dephosphorylated and sequestered to the microtubules. The phosphorylation of BimEL in mitosis is crucial because it keeps the protein in an inactive state, as it was seen that induction of BimEL dephosphorylation leads to apoptosis. The kinase responsible for this phosphorylation is ERK5, a MAPK family member. However, the aminoacid residues undergoing phosphorylation remain to be identified. One of this project's goals was to identify these residues. In order to do that, some putative BimEL phospho-residues where chosen and mutated into non-phosphorylatable residues. These mutants will latter on be used in in vitro kinase assays aiming to identify the BimEL residues that undergo phosphorylation in mitosis. Another of this project's goals was to create a working model in yeast (Saccharomyces cerevisiae) that would allow us to continue the studies of BimEL's phosphorylation during mitosis. As yeast don't have endogenous BimEL or ERK5, the genes codifying these proteins were cloned into yeast expression plasmids and introduced in yeast cells. The two proteins were expressed and their phosphorylation state in mitosis was investigated. Neither protein was phosphorylated, which means the system needs to be remodelled in order to induce the phosphorylation of BimEL by alternative pathways
Autores principais:Santos, Daniela Vanessa Moutinho dos, 1984-
Assunto:Biologia molecular Apoptose Mitose Fosforilação Teses de mestrado
Ano:2007
País:Portugal
Tipo de documento:dissertação de mestrado
Tipo de acesso:acesso aberto
Instituição associada:Universidade de Lisboa
Idioma:português
Origem:Repositório da Universidade de Lisboa

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