title: Profilin-PTEN interaction suppresses NF-κB activation via inhibition of IKK phosphorylation.
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.
authors.affiliation: Laboratory of Immunology, Centre for DNA Fingerprinting & Diagnostics, Nampally, Hyderabad 500 001, Telangana, India Graduate Studies, Manipal University, Manipal 576104, Karnataka, India.
authors.forename: Adeel H
authors.initials: AH
authors.lastname: Zaidi
authors.affiliation: Laboratory of Immunology, Centre for DNA Fingerprinting & Diagnostics, Nampally, Hyderabad 500 001, Telangana, India manna@cdfd.org.in.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Manna
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D051304:Profilins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C495738:PFN1 protein, human; D051304:Profilins; C498143:RELA protein, human; D051996:Transcription Factor RelA; D025521:Tumor Suppressor Proteins; D051550:I-kappa B Kinase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
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)