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

Adeel H. Zaidi, Sunil K. Manna

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The molecular mechanism of Profilin for its tumour suppressor activity is still unknown. Nuclear transcription factor κB (NFκB) 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 NFκB, which might repress the tumorigenic response. Profilin overexpressing cells show low basal activity of IκBα kinase (IKK), high amounts of cytoplasmic inhibitory subunit of NFκB (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.

Original languageEnglish (US)
Pages (from-to)859-872
Number of pages14
JournalBiochemical Journal
Volume473
Issue number7
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

Keywords

  • Inhibitory subunit of nf-κB (iκBα)
  • Iκbα
  • Kinase (IKK)
  • Nuclear transcription factor κB (NF-κB)
  • Phosphatase and tension homologue (PTEN)
  • Profilin
  • Tumour necrosis factor (TNF)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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