Profilin-PTEN interaction suppresses NF-κB activation via inhibition of IKK phosphorylation

The molecular mechanism of Profilin for its tumour suppressor activity is still unknown. Nuclear transcription factor kappa B (NF-kappa B) is known to activate many target genes involved in cell proliferation. In the present study, we provide evidence that supports the involvement of Profilin in regulation of NF-kappa B, which might repress the tumorigenic response. Profilin overexpressing cells show low basal activity of I kappa B alpha kinase (IKK), high amounts of cytoplasmic inhibitory subunit of NF-kappa B (I kappa B alpha) and p65, and low nuclear NF-kappa B DNA binding activity. Co-localization and co-immunoprecipitation (Co-IP) studies suggest that Profilin interacts with a protein phosphatase, phosphatase and tension homologue (PTEN), and protects it from degradation. In turn, PTEN interacts physically and maintains a low phosphorylated state of the IKK complex and thereby suppresses NF-kappa B signalling. Thus, Profilin overexpressing cells show a decrease in NF-kappa B activation mediated by most of the inducers and potentiate cell death by repressing NF-kappa B-dependent genes involved in cell cycle progression. For the first time, we provide evidence, which suggests that Profilin increases tumour suppressor activity by regulating NF-kappa B.