Regulation of the NF-kappaB alternative pathway: implication for B cell transformation
Lavorgna, Alfonso (2008) Regulation of the NF-kappaB alternative pathway: implication for B cell transformation. [Tesi di dottorato] (Inedito)
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The NF-B2 gene is recurrently mutated and over-expressed in human lymphoid malignancies. However, a casual relationship between NF-B2 mutation and lymphomagenesis has not been established. It is also unclear how the mutation may lead to lymphoid malignancies. Recent studies suggest that nuclear factor B inducing kinase (NIK) is suppressed through constitutive proteasome-mediated degradation regulated by TRAF3, thus preventing processing of the NF-B2 precursor protein p100 to release p52. Here we demonstrate that BAFF Receptor, a member of the TNF Receptor family, interact with TRAF1, a member of TRAF family. This interaction activates NF-B2 via increased degradation of TRAF3 and stabilization of NIK. Indeed, interference of TRAF1 in lymphoma B cell line downregulates p100 processing and lead to decreased survival of B cells.
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