Glycogen Synthase Kinase-3β Regulates NF-κB1/p105 Stability*
By F. Demarchi, C. Bertoli, P. Sandy, C. Schneider. Journal of Biological Chemistry, 2003
140 citations recorded by the source corpus.
A number of different kinases have been implicated in NF-κB regulation and survival function. Here we investigated the molecular cross-talk between glycogen synthase kinase-3β (GSK-3β) and the p105 precursor of the NF-κB p50 subunit. GSK-3β forms an in vivo complex with and specifically phosphorylates NF-κB1/p105 at Ser-903 and Ser-907 in vitro. In addition, the p105 phosphorylation level is reduced in fibroblasts lacking GSK-3β as compared with wild-type cells. GSK-3β has a dual effect on p105: it stabilizes p105 under resting conditions and primes p105 for degradation upon tumor necrosis factor (TNF)-α treatment. Indeed, constitutive processing of p105 to p50 occurs at a higher rate in cells lacking GSK-3β with respect to wild-type cells and can be reduced upon reintroduction of GSK-3β by transfection. Moreover, p105 degradation in response to TNF-α is prevented in GSK-3β–/– fibroblasts and by a Ser to Ala point mutation on p105 at positions 903 or 907. Interestingly, the increased sensitiveness to TNF-α-induced death occurring in GSK-3β–/– fibroblasts, which is coupled to a perturbation of p50/105 ratio, can be reproduced by p105 silencing in wild-type fibroblasts.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/b36ce4613ad805757b72b07bafbc9ec4f7a0e047
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Citations in the corpus
- Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway (2006, background): “This stabilizes p105 but is required for subsequent inducible p105 processing in response to TNF stimulation (Demarchi et al., 2003).”