Upregulated RIP3 Expression Potentiates MLKL Phosphorylation-Mediated Programmed Necrosis in Toxic Epidermal Necrolysis

The Journal of Investigative Dermatology
Sue Kyung KimYou-Sun Kim

Abstract

Toxic epidermal necrolysis (TEN) is a severe adverse drug reaction involving extensive keratinocyte death in the epidermis. Histologically, the skin from TEN patients exhibits separation at the dermo-epidermal junction and accompanying necrosis of epidermal keratinocytes. Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is an essential part of the cellular machinery that executes "programmed", or "regulated", necrosis and has a key role in spontaneous cell death and inflammation in keratinocytes under certain conditions. Here we show that RIP3 expression is highly upregulated in skin sections from TEN patients and may therefore contribute to the pathological damage in TEN through activation of programmed necrotic cell death. The expression level of mixed lineage kinase domain-like protein (MLKL), a key downstream component of RIP3, was not significantly different in skin lesions of TEN. However, elevated MLKL phosphorylation was observed in the skin from TEN patients, indicating the presence of RIP3-dependent programmed necrosis. Importantly, in an in vitro model of TEN, dabrafenib, an inhibitor of RIP3, prevented RIP3-mediated MLKL phosphorylation and decreased cell death. Results from this study suggest that the high exp...Continue Reading

References

Apr 1, 1997·Nitric Oxide : Biology and Chemistry·K D KrönckeV Kolb-Bachofen
Jan 17, 2007·Journal of the American Academy of Dermatology·Frederick A PereiraDavid M Rosmarin
Jul 12, 2007·Clinical Journal of Oncology Nursing·Lisa Hartkopf Smith
Apr 15, 2008·Nature Chemical Biology·Alexei DegterevJunying Yuan
Jul 28, 2009·Cell·Wim DeclercqPeter Vandenabeele
Sep 2, 2009·The Journal of Experimental Medicine·Andrew KovalenkoDavid Wallach
Nov 17, 2009·Indian Journal of Dermatology, Venereology and Leprology·Timir Y MehtaRamesh K Goyal
Dec 30, 2009·The Journal of Cell Biology·Peter GeserickMartin Leverkus
Sep 9, 2010·Nature Reviews. Molecular Cell Biology·Peter VandenabeeleGuido Kroemer
Mar 4, 2011·Nature·William J KaiserEdward S Mocarski
Sep 16, 2011·Epilepsy Research·Sae-Hoon KimUNKNOWN Adverse Drug Reaction Research Group in Korea
Oct 4, 2011·Critical Reviews in Oncology/hematology·Wei WuJianyong Li
Nov 15, 2011·Cell Death and Differentiation·N VanlangenakkerP Vandenabeele
Dec 16, 2011·Journal of the American Academy of Dermatology·Andrew DowneyAlan Cooper
Feb 11, 2012·The Journal of Allergy and Clinical Immunology·Chun-Yu WeiShuen-Iu Hung
Mar 17, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jie ZhaoZheng-Gang Liu
Nov 12, 2013·Cell Reports·Diana Panayotova-DimitrovaMartin Leverkus
Dec 11, 2013·The American Journal of Gastroenterology·Maria PierdomenicoSalvatore Cucchiara
Jul 1, 2007·Medical Journal, Armed Forces India·S Grover

❮ Previous
Next ❯

Citations

Jan 19, 2016·Nature Reviews. Drug Discovery·Marcus ConradBrent R Stockwell
Jul 16, 2015·The Journal of Investigative Dermatology·Diana Panayotova-DimitrovaMartin Leverkus
Apr 8, 2016·Cellular and Molecular Life Sciences : CMLS·Tom Vanden BerghePeter Vandenabeele
Feb 27, 2016·Cell Death and Differentiation·Z SuY Chen
Oct 21, 2016·Expert Opinion on Therapeutic Patents·Spandana Rajendra KopalliSushruta Koppula
Dec 16, 2016·Immunology and Cell Biology·Inbar ShlomovitzMotti Gerlic
May 13, 2017·Cell Death and Differentiation·Sasker GrootjansPeter Vandenabeele
Nov 7, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaoliang WangHans-Uwe Simon
Jun 5, 2018·Experimental Dermatology·Leopold Eckhart, Erwin Tschachler
Nov 12, 2019·Journal of Clinical Pharmacology·Abdelbaset A ElzagallaaiMichael J Rieder
Sep 22, 2018·Experimental & Molecular Medicine·Han-Hee ParkYou-Sun Kim
Apr 26, 2019·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Teresa Bellón
May 30, 2015·Cell Death and Differentiation·D A RodriguezD R Green
Jan 1, 2015·F1000Research·James M Murphy, James E Vince
Mar 31, 2020·Journal of Neuro-oncology·Guilherme Afonso VergaraRicardo Weinlich
Jun 15, 2019·International Journal of Molecular Medicine·Yuping LiuYi Wang
Nov 14, 2019·Cell Death & Disease·Tamás MolnárGábor Koncz
Sep 9, 2020·Annals of the Rheumatic Diseases·Jimin JeonYou-Sun Kim
Sep 18, 2020·Seminars in Cell & Developmental Biology·Lin Liu, Najoua Lalaoui
Jan 19, 2020·The Journal of Allergy and Clinical Immunology. in Practice·Akito HasegawaRiichiro Abe
Nov 8, 2020·Current Opinion in Immunology·Ashley WeirJames E Vince
Sep 30, 2021·Experimental and Therapeutic Medicine·Yongsam JoDeug Y Shin

❮ 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.