MPB, a novel berberine derivative, enhances lysosomal and bactericidal properties via TGF-β-activated kinase 1-dependent activation of the transcription factor EB

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Xiaojia LiuHongbin Deng

Abstract

Lysosome has a crucial role in clearance of endocytosed pathogens from the cell. Small molecules that can boost lysosome function and bactericidal ability to cope with subsequent infection are urgently needed. Here, we report that MPB, a novel berberine derivative, induced lysosome-based degradation and clearance of methicillin-resistant Staphylococcus aureus and enteroinvasive Escherichia coli in macrophages. MPB caused nuclear translocation of transcription factor EB (TFEB), which boosted expression of lysosome genes. TFEB silencing repressed the MPB-mediated enhancements in degradation and bacterial eradication. MPB switched on TFEB nuclear translocation by coupling 2 parallel signaling pathways. MPB-triggered JNK activation led to 14-3-3δ being released from TFEB, which, in turn, caused TFEB nuclear translocation. In addition, MPB induced AMPK activation and subsequent inhibition of mechanistic target of rapamycin activity, which also contributed to TFEB nuclear translocation. Importantly, genetical or pharmaceutical inhibition of TGF-β-activated kinase 1 (TAK1) reduced MPB action remarkably. MPB acted through TAK1 at lysine 158 to activate JNK and AMPK and, thus, induced TFEB-dependent bactericidal activity in macrophages....Continue Reading

References

Jul 19, 2001·Nature·C WangZ J Chen
Feb 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Reuben J ShawLewis C Cantley
Mar 26, 2004·Nature Reviews. Microbiology·James B KaperHarry L Mobley
Sep 28, 2005·Nature Immunology·Shintaro SatoShizuo Akira
Aug 8, 2006·Current Opinion in Pharmacology·Alexandra K MarrRobert Ew Hancock
Nov 7, 2006·Proceedings of the National Academy of Sciences of the United States of America·Min XieMichael D Schneider
Sep 2, 2008·Nature Cell Biology·Alessandro SorrentinoMaréne Landström
Sep 25, 2008·Nature Reviews. Molecular Cell Biology·Jason M Kinchen, Kodi S Ravichandran
Jun 27, 2009·Science·Marco SardielloAndrea Ballabio
Oct 22, 2009·Science Signaling·Kohsuke YamazakiJun-ichiro Inoue
May 28, 2011·Science·Carmine SettembreAndrea Ballabio
Jul 15, 2011·Human Molecular Genetics·Michela PalmieriAndrea Ballabio
Sep 6, 2011·Developmental Cell·Diego L MedinaAndrea Ballabio
Feb 22, 2012·The EMBO Journal·Carmine SettembreAndrea Ballabio
Apr 3, 2012·Molecular and Cellular Probes·Mar LarrosaMaría Teresa García-Conesa
May 9, 2012·Trends in Immunology·Gregory D Fairn, Sergio Grinstein
Jun 14, 2012·Science Signaling·Agnes Roczniak-FergusonShawn M Ferguson
Sep 4, 2012·IUBMB Life·Liang DaiPeter C F Cheung
Apr 24, 2013·Nature Reviews. Molecular Cell Biology·Carmine SettembreAndrea Ballabio
May 8, 2013·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Anne-Catrin UhlemannFrank R DeLeo
May 11, 2013·Science·Leigh A BaxtMarcia B Goldberg
Jul 23, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Behnam SaberiNeil Kaplowitz
Aug 7, 2013·Journal of Molecular Cell Biology·Hanna AppelqvistKarin Öllinger
Dec 18, 2013·Cell Research·Ryan C RussellKun-Liang Guan
Jan 22, 2014·Nature Reviews. Immunology·Tracy Hussell, Thomas J Bell
Jul 2, 2014·The Journal of Clinical Investigation·Sayaka Inokuchi-ShimizuEkihiro Seki
May 25, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Diego Ploper, Edward M De Robertis
Dec 17, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ali VuralJohn H Kehrl
Jun 3, 2016·Journal of Cell Science·Gennaro Napolitano, Andrea Ballabio
Aug 9, 2016·Annual Review of Cell and Developmental Biology·Rushika M Perera, Roberto Zoncu
Aug 26, 2016·Immunological Reviews·Roni LevinJohnathan Canton
Sep 13, 2016·Nature Cell Biology·Yang LiChonglin Yang
Oct 28, 2016·The Biochemical Journal·Helen R HeathcoteIan P Salt
Jan 6, 2017·Autophagy·Silvia Vega-Rubin-de-CelisJames Brugarolas

❮ Previous
Next ❯

Citations

Apr 27, 2020·Frontiers of Medicine·Danyang SongDaiming Fan
Dec 18, 2020·Frontiers in Cellular and Infection Microbiology·Kuldeep Sachdeva, Varadharajan Sundaramurthy
Nov 9, 2021·Frontiers in Immunology·Mumin OzturkSuraj P Parihar

❮ 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.