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

Zaidi, Adeel Husain (2016) Profilin-PTEN interaction suppresses NF-KB 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. Nuclear transcription factor κB (NF-κB) 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-κB, which might repress the tumorigenic response. Profilin overexpressing cells show low basal activity of IκBα kinase (IKK), high amounts of cytoplasmic inhibitory subunit of NF-κB (IκBα) and p65, and low nuclear NF-κB 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-κB signalling. Thus, Profilin overexpressing cells show a 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 evidence, which suggests that Profilin increases tumour suppressor activity by regulating NF-κB.

Item Type: Article
Uncontrolled Keywords: IκBα kinase (IKK); Profilin; inhibitory subunit of NF-κB (IκBα); nuclear transcription factor κB (NF-κB); phosphatase and tension homologue (PTEN); tumour necrosis factor (TNF).
Subjects: Research > Research Center - Health Sciences
Depositing User: KMC Library
Date Deposited: 04 Oct 2016 15:50
Last Modified: 04 Oct 2016 15:50
URI: http://eprints.manipal.edu/id/eprint/147000

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