Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2-Keap1 interaction: Activation of antioxidative pathway in papillary thyroid carcinoma

Head & Neck
Debora Lucia Seguro DanilovicSuemi Marui

Abstract

Nuclear factor erythroid 2-like 2 (NFE2L2) encodes Nrf2, transcription factor of antioxidative genes. In the presence of reactive oxygen species, Keap1 (Kelch-ECH-associating protein-1) inhibitor complex undergoes conformational changes disrupting Keap1-Nrf2 binding and Nrf2 translocates into nucleus. We evaluated the presence of mutations in NFE2L2 and KEAP1 in papillary thyroid carcinomas (PTCs) and correlated them with clinical presentation. Coding regions of NFE2L2 and KEAP1 were sequenced in 131 patients with PTC. Clinical and histopathological features were analyzed. Immunohistochemical analysis of Nrf2 expression was performed in mutated carcinomas. Although no mutations were found in NFE2L2, missense mutations in KEAP1 were observed in 6 patients with PTC (4.6%). Immunohistochemistry showed increased Nrf2 expression in nuclei of all mutated carcinomas, which presented poor prognostic features in histopathology. We identified mutations in KEAP1 associated with Nrf2 overexpression in PTC. Mutations favored disruption of inhibitory interaction Nrf2-Keap1 to enable increased antioxidant Nrf2 activity, possibly with prognostic consequences.

References

Aug 31, 2002·Nucleic Acids Research·Vasily RamenskyShamil Sunyaev
Feb 7, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nobunao WakabayashiPaul Talalay
Oct 6, 2006·PLoS Medicine·Anju SinghShyam Biswal
Sep 8, 2007·Biochemical and Biophysical Research Communications·Paul Nioi, Truyen Nguyen
Sep 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Tatsuhiro ShibataSetsuo Hirohashi
Mar 27, 2009·Trends in Biochemical Sciences·John D Hayes, Michael McMahon
May 7, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shinsuke HommaMasayuki Yamamoto
Dec 8, 2009·The Journal of Pathology·Yoo Ri KimSug Hyung Lee
Dec 19, 2009·Toxicologic Pathology·James E KlaunigBarbara A Hocevar
Mar 10, 2010·Journal of Surgical Oncology·Tsuyoshi TakahashiHiromi Wada
Aug 3, 2010·Nature Methods·Jana Marie SchwarzDominik Seelow
Jan 21, 2011·Journal of Human Genetics·Qing Kay LiEdward Gabrielson
Jan 22, 2011·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Keiko TaguchiMasayuki Yamamoto
Jun 17, 2011·Cancer Research·Panagiotis A KonstantinopoulosStephen A Cannistra
Oct 12, 2012·PloS One·Yongwook ChoiAgnes P Chan
Apr 11, 2013·JAMA : the Journal of the American Medical Association·Mingzhao XingVlasta Sykorova
Jun 15, 2013·The Journal of Clinical Endocrinology and Metabolism·Panos G ZirosGerasimos P Sykiotis
Jan 29, 2014·European Journal of Endocrinology·Debora L S DanilovicSuemi Marui
Jul 16, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mingzhao XingJustin Bishop
Oct 12, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Curtis R PickeringMitchell J Frederick
Oct 23, 2014·Journal of Cancer Prevention·Jae Hong NoYong Sang Song
Jan 16, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jaana M HartikainenArto Mannermaa
Oct 30, 2015·European Journal of Endocrinology·Catarina TavaresManuel Sobrinho-Simões
Jun 7, 2016·Trends in Molecular Medicine·Silvia MenegonSilvia Giordano
Oct 6, 2016·Frontiers in Endocrinology·Eijun NishiharaAkira Miyauchi

❮ Previous
Next ❯

Citations

Jul 22, 2020·Thyroid : Official Journal of the American Thyroid Association·Panos G ZirosGerasimos P Sykiotis
May 18, 2019·Oxidative Medicine and Cellular Longevity·Emiliano Panieri, Luciano Saso
Jan 29, 2020·Antioxidants & Redox Signaling·Katarína SmolkováPéter Bai
Aug 21, 2019·Frontiers in Endocrinology·Cedric O RenaudGerasimos P Sykiotis
Jan 7, 2021·Antioxidants & Redox Signaling·Emiliano Panieri, Luciano Saso
Nov 8, 2020·Antioxidants·Christina ThanasGerasimos P Sykiotis

❮ 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.

© 2022 Meta ULC. All rights reserved