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Zaidi, A.H. and Manna, S.K. (2016) Profilin-PTEN interaction suppresses NF-kappa B activation via inhibition of IKK phosphorylation. Biochemical Journal, 473 (7). pp. 859-872. ISSN 0264-6021

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Abstract

The molecular mechanism of Profilin for its tumour suppressor activity is still unknown. NF-κB is known to activate many target genes involved in cell proliferation. In this study, we provide evidences that support the involvement of Profilin in regulation of NF-κB, which might repress the tumourigenic response. Profilin overexpressing cells show low basal activity of IKK, high amount of cytoplasmic IκBα and p65, and low nuclear NF-κB DNA binding activity. Co-localisation and co-immunoprecipitation studies suggest that Profilin interacts with a protein phosphatase, PTEN and protects it from degradation. In turn, PTEN interacts physically and maintains low phosphorylated state of IKK complex and thereby suppresses NF-κB signalling. Thus, Profilin-overexpressing cells show decrease in NF-κB activation mediated by most of the inducers and potentiate cell death by repressing NF-κB-dependent genes involved in cell cycle progression. For the first time, we provide evidences, which suggest that Profilin increases tumour suppressor activity by regulating NF-κB.

Item Type: Article
Depositing User: Dr P Divakar
Date Deposited: 25 Jan 2016 06:07
Last Modified: 19 Oct 2017 19:20
URI: http://cdfd.sciencecentral.in/id/eprint/697

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