ESCRT proteins restrict constitutive NF-κB signaling by trafficking cytokine receptors

Science Signaling
Agnieszka MamińskaMarta Miaczynska

Abstract

Because signaling mediated by the transcription factor nuclear factor κB (NF-κB) is initiated by ligands and receptors that can undergo internalization, we investigated how endocytic trafficking regulated this key physiological pathway. We depleted all of the ESCRT (endosomal sorting complexes required for transport) subunits, which mediate receptor trafficking and degradation, and found that the components Tsg101, Vps28, UBAP1, and CHMP4B were essential to restrict constitutive NF-κB signaling in human embryonic kidney 293 cells. In the absence of exogenous cytokines, depletion of these proteins led to the activation of both canonical and noncanonical NF-κB signaling, as well as the induction of NF-κB-dependent transcriptional responses in cultured human cells, zebrafish embryos, and fat bodies in flies. These effects depended on cytokine receptors, such as the lymphotoxin β receptor (LTβR) and tumor necrosis factor receptor 1 (TNFR1). Upon depletion of ESCRT subunits, both receptors became concentrated on and signaled from endosomes. Endosomal accumulation of LTβR induced its ligand-independent oligomerization and signaling through the adaptors TNFR-associated factor 2 (TRAF2) and TRAF3. These data suggest that ESCRTs constit...Continue Reading

References

Jul 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·C B KimmelT F Schilling
Oct 16, 1999·The Journal of Biological Chemistry·H SakuraiW Toriumi
Aug 6, 2003·The Journal of Cell Biology·Kristi G BacheHarald Stenmark
Jun 1, 2004·Molecular and Cellular Biology·Ricardo G CorreaInder M Verma
Jun 25, 2004·Nucleic Acids Research·Andreas HenschelBianca Habermann
Jun 26, 2004·The Journal of Biological Chemistry·Melissa D StuchellWesley I Sundquist
Jan 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Kwang-Min ChoeKathryn V Anderson
Jul 30, 2005·Current Biology : CB·Ricardo G CorreaInder M Verma
Sep 17, 2005·Science·Markus W CovertDavid Baltimore
Jan 5, 2007·Annual Review of Immunology·Bruno Lemaitre, Jules Hoffmann
Nov 23, 2007·Experimental Cell Research·Camilla RaiborgHarald Stenmark
Jan 15, 2008·Nature Protocols·Christine Thisse, Bernard Thisse
Jan 23, 2008·The Journal of Cell Biology·Phyllis I HansonJohn E Heuser
Oct 22, 2008·Experimental Cell Research·Lukasz SadowskiMarta Miaczynska
Mar 28, 2009·Nature·Camilla Raiborg, Harald Stenmark
Aug 22, 2009·Nature Reviews. Molecular Cell Biology·Alexander Sorkin, Mark von Zastrow
Mar 2, 2010·Nature·Claudio CollinetMarino Zerial
Mar 18, 2010·BMC Research Notes·Mark de JongTimo M Breit
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Eiji MoritaWesley I Sundquist
Sep 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Farshid S GarmaroudiBruce M McManus
Sep 16, 2010·Journal of Cell Science·Oscar Marino VidalMartin P Zeidler
Nov 26, 2010·Cell Research·Vincent Feng-Sheng ShihAlexander Hoffmann
Jul 16, 2011·Current Biology : CB·Flavia StefaniPhilip Woodman
Jul 19, 2011·Developmental Cell·William M HenneScott D Emr
Jul 21, 2011·Nature Immunology·David Baltimore
Oct 25, 2011·Immunological Reviews·Carl F Ware
Nov 17, 2011·Seminars in Cell & Developmental Biology·Pauline GonnordChristophe Lamaze
Dec 14, 2011·Cytokine & Growth Factor Reviews·Caroline RemouchampsEmmanuel Dejardin
Feb 3, 2012·Physiological Reviews·Sara SigismundPier Paolo Di Fiore
Feb 4, 2012·Genes & Development·Matthew S Hayden, Sankar Ghosh
Mar 13, 2012·Structure·Monica AgromayorRoger L Williams
Mar 15, 2012·Science Signaling·Ben BrankatschkJean Gruenberg
Mar 23, 2012·Immunological Reviews·Shao-Cong Sun

❮ Previous
Next ❯

Citations

Oct 14, 2017·PLoS Genetics·Steven J Del SignoreAvital A Rodal
Jun 23, 2018·PLoS Genetics·Xènia Crespo-YàñezMarie-Odile Fauvarque
Jun 8, 2018·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Guillaume DesrochersArnim Pause
Nov 5, 2016·PloS One·Raphaële ThiébautVincent Ollendorff
Sep 1, 2018·The EMBO Journal·João Vaz-SilvaClarissa L Waites
Jan 14, 2020·EMBO Molecular Medicine·Ewelina SzymańskaMarta Miączyńska
Aug 1, 2019·Science Signaling·Chih Hung LoJonathan N Sachs
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Eunji JungJoon Kim
Jun 13, 2018·International Journal of Molecular Sciences·Sarah E VandalS Tariq Ahmad
Dec 28, 2019·Cell Communication and Signaling : CCS·Magdalena Banach-OrłowskaMarta Miączyńska
Jul 8, 2020·International Journal of Molecular Sciences·Chia-Chun TsengShun-Jen Chang
Jun 6, 2017·Nature Reviews. Immunology·Shao-Cong Sun
Mar 16, 2019·Cellular & Molecular Immunology·Lei ZhangXian C Li
Nov 9, 2018·Molecular Neurobiology·Marcelina FirkowskaJacek Jaworski
Jan 10, 2021·Journal of Cell Science·Krzysztof KolmusMarta Miączyńska
Dec 15, 2020·Toxicology Letters·Arnab MaitiAlok Kumar Sil
Dec 6, 2020·The Journal of Biological Chemistry·Alexandra M WhiteleyDaniel Finley
Nov 6, 2020·Cell Communication and Signaling : CCS·Małgorzata MaksymowiczMagdalena Banach-Orłowska
Jun 8, 2021·Cell Calcium·Alejandro Marmolejo-Garza, Amalia M Dolga
Aug 3, 2021·Virus Research·Mei HeCheng-Qiang He

❮ 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.