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.
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The human immunodeficiency virus in the bloodstream. In this issue Klug et al. (pages 911–918) demonstrate the potential role of the gp41 pocket-binding domain of HIV protein gp160 in mediating membrane fusion and in immune modulation. - PDF Icon PDF LinkFront Matter
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Research Article|
March 29 2016
Profilin–PTEN interaction suppresses NF-κB activation via inhibition of IKK phosphorylation
Adeel H. Zaidi;
Adeel H. Zaidi
*Laboratory of Immunology, Centre for DNA Fingerprinting & Diagnostics, Nampally, Hyderabad 500 001, Telangana, India
†Graduate Studies, Manipal University, Manipal 576104, Karnataka, India
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Sunil K. Manna
Sunil K. Manna
1
*Laboratory of Immunology, Centre for DNA Fingerprinting & Diagnostics, Nampally, Hyderabad 500 001, Telangana, India
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
May 29 2015
Revision Received:
January 04 2016
Accepted:
January 19 2016
Accepted Manuscript online:
January 19 2016
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 Authors; published by Portland Press Limited
2016
Biochem J (2016) 473 (7): 859–872.
Article history
Received:
May 29 2015
Revision Received:
January 04 2016
Accepted:
January 19 2016
Accepted Manuscript online:
January 19 2016
Citation
Adeel H. Zaidi, Sunil K. Manna; Profilin–PTEN interaction suppresses NF-κB activation via inhibition of IKK phosphorylation. Biochem J 1 April 2016; 473 (7): 859–872. doi: https://doi.org/10.1042/BJ20150624
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