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

The Biochemical Journal
Adeel H Zaidi, Sunil K Manna

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.

References

May 18, 2001·The Journal of Biological Chemistry·J A GustinD B Donner
Feb 26, 2003·Cell·Thomas D Pollard, Gary G Borisy
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Oct 12, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kamel IzeradjeneJanet A Houghton
Dec 14, 2004·The Journal of Biological Chemistry·Sunil K Manna, Govindarajan T Ramesh
Sep 22, 2005·Nature Reviews. Immunology·Michael Karin, Florian R Greten
Mar 16, 2007·Clinical Oncology : a Journal of the Royal College of Radiologists·R O EscárcegaA Zamora
Jul 16, 2008·Immunologic Research·Laura A Solt, Michael J May
Oct 22, 2008·Journal of Cellular Physiology·Tuhin DasPartha Roy
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Feb 6, 2010·The Journal of Biological Chemistry·Sunil K MannaChitta Sureshkumar
May 3, 2011·Nature Cell Biology·Subbareddy MaddikaJunjie Chen
Feb 4, 2012·Genes & Development·Matthew S Hayden, Sankar Ghosh
Nov 1, 2013·British Journal of Pharmacology·Nune Raviprakash, Sunil Kumar Manna
Jan 1, 2014·EMBO Reports·Michael Hinz, Claus Scheidereit
Mar 26, 2014·Biochemical and Biophysical Research Communications·Ye Na ChoiSoon Ji Yoo

❮ Previous
Next ❯

Citations

Jan 29, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Federica Scotto di CarloFernando Gianfrancesco
Jun 27, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Stuart H Ralston
Jul 15, 2020·Biophysics Reviews·Rhonda J Davey, Pierre Dj Moens
Jul 22, 2018·Biophysics Reviews·Joelle V F CoumansPierre D J Moens
Feb 17, 2021·Molecular Biology Reports·Chang-Jin LeeYoun-Jung Kang
Feb 19, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Zhe WeiHua Yue
Jul 9, 2021·Frontiers in Cell and Developmental Biology·Faliang WangJieya Shao

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.