FKBP4 integrates FKBP4/Hsp90/IKK with FKBP4/Hsp70/RelA complex to promote lung adenocarcinoma progression via IKK/NF-κB signaling.

Cell Death & Disease
Shuai ZongYueran Zhao

Abstract

FKBP4 belongs to the family of immunophilins, which serve as a regulator for steroid receptor activity. Thus, FKBP4 has been recognized to play a critical role in several hormone-dependent cancers, including breast and prostate cancer. However, there is still no research to address the role of FKBP4 on lung adenocarcinoma (LUAD) progression. We found that FKBP4 expression was elevated in LUAD samples and predicted significantly shorter overall survival based on TCGA and our cohort of LUAD patients. Furthermore, FKBP4 robustly increased the proliferation, metastasis, and invasion of LUAD in vitro and vivo. Mechanistic studies revealed the interaction between FKBP4 and IKK kinase complex. We found that FKBP4 potentiated IKK kinase activity by interacting with Hsp90 and IKK subunits and promoting Hsp90/IKK association. Also, FKBP4 promotes the binding of IKKγ to IKKβ, which supported the facilitation role in IKK complex assembly. We further identified that FKBP4 TPR domains are essential for FKBP4/IKK interaction since its association with Hsp90 is required. In addition, FKBP4 PPIase domains are involved in FKBP4/IKKγ interaction. Interestingly, the association between FKBP4 and Hsp70/RelA favors the transport of RelA toward the n...Continue Reading

References

Mar 16, 2000·Breast Cancer Research and Treatment·B K WardT Ratajczak
Dec 26, 2001·The Journal of Biological Chemistry·Todd H DaviesEdwin R Sánchez
Feb 28, 2002·Molecular Cell·Guoqing ChenDavid V Goeddel
Dec 23, 2003·Journal of Cellular Biochemistry·Junghan Suh, Arnold B Rabson
Aug 27, 2004·Nature·Eli PikarskyYinon Ben-Neriah
Aug 21, 2007·Cell Cycle·Hana BlazkovaDirk A Dobbelaere
Aug 28, 2007·International Journal of Cancer. Journal International Du Cancer·Jian-Feng LinFu-Kun Zhao
Oct 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey T IrelanSumit K Chanda
Oct 27, 2007·The EMBO Journal·Benjamin Barré, Neil D Perkins
Nov 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Georgios T StathopoulosTimothy S Blackwell
May 31, 2008·Nature Reviews. Cancer·Phillip J GrayStuart K Calderwood
Jul 9, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Caroline DesmetzJerome Solassol
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Béatrice ChambraudEtienne-Emile Baulieu
Apr 26, 2011·Current Opinion in Pharmacology·Jérôme SolassolThierry Maudelonde
Sep 6, 2011·Trends in Endocrinology and Metabolism : TEM·Cheryl L StorerMarc B Cox
Jun 14, 2013·PloS One·Christin KlenkeChristian Kaltschmidt
Jan 24, 2014·Biochemical Society Transactions·Adeline C Ledoux, Neil D Perkins
Jul 25, 2014·Nature Reviews. Cancer·Zhao ChenKwok-Kin Wong
Oct 25, 2016·Trends in Cell Biology·Dae In Kim, Kyle J Roux
Mar 3, 2017·Molecular Oncology·Jugal Bharat JoshiJaideep Chaudhary
Jun 2, 2017·Trends in Biochemical Sciences·Peter Lönn, Ulf Landegren
Jan 25, 2018·Nature·Roy S HerbstChris Boshoff
Mar 9, 2018·Current Protocols in Protein Science·Kyle J RouxDanielle G May
Dec 21, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shengnan HuYueran Zhao
Jan 9, 2019·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Feb 6, 2019·Biomolecules·Nadia R ZgajnarMario D Galigniana
May 3, 2019·Journal of Cellular and Molecular Medicine·Linying SunYueran Zhao
Nov 23, 2019·Biochemical Society Transactions·Cristina Daneri-BecerraMario D Galigniana

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Software Mentioned

SPSS
GraphPad Prism
DEGseq2 R
MedCalc

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.