MEKK1 and MEKK3 involvement in TNF-alpha signalling in cervical carcinoma hela cells
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Göktuna, Serkan İsmail (2005) MEKK1 and MEKK3 involvement in TNF-alpha signalling in cervical carcinoma hela cells. [Thesis]
Official URL: http://risc01.sabanciuniv.edu/record=b1147834 (Table of Contents)
In this study, we have investigated the role of MEKK1 and MEKK3 in response to tumor necrosis factor-alpha (TNF-alpha) induction. It was known that MEKK1 and MEKK3 are good candidates for this moderation and they have been already shown to act in the downstream of TNF-alpha signaling or related cytokine responses. Far these reasons, we studied MAPK activities and nuclear factor-kappaB (NF-kappaB) activation in response to TNF-alpha induction in the presence and in the absence of MEKK1 and MEKK3 to ascertain their involvement in the overall picture. In untransfected cells, we obtained MAPK profiles upon TNF-alpha treatment JNK. p38 and ERK MAP kinases activation profiles via phosphorylation was obtained. Then we observed NF-kappaB activation via IkappaB subunit degradation. In older to activate or exclude MAP3K molecules, continuously active and dominant negative forms of the MEKK1 and MEKK3 were overexpressed to understand their role on MAPK activities and NF-kappaB activation in cervical carcinoma HeLa cells. MEKK1 was found to be involved as the moderator of the TNF-alpha signaling in the upstream of MAP kinases. Termination of JNK phosphorylation in dominant negative MEKKl overexpression was a good evidence for this phenomenon. On the other hand, MEKK3 overexpression gave us clues about its functional similarity to MEKKl in this system but these results should be clarified with further experimentation. Our findings suggest that both MEKKl and MEKK3 are involved in the TNF-alpha signaling in the upstream of MAPKs and NF-kappaB which is an important result to understand the nature of signaling events in cell death or cell survival
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