ATG5 Promotes Death Signaling in Response to the Cyclic Depsipeptides Coibamide A and Apratoxin A.

Marine Drugs
Xuemei WanJane E Ishmael

Abstract

Our understanding of autophagy and lysosomal function has been greatly enhanced by the discovery of natural product structures that can serve as chemical probes to reveal new patterns of signal transduction in cells. Coibamide A is a cytotoxic marine natural product that induces mTOR-independent autophagy as an adaptive stress response that precedes cell death. Autophagy-related (ATG) protein 5 (ATG5) is required for coibamide-induced autophagy but not required for coibamide-induced apoptosis. Using wild-type and autophagy-deficient mouse embryonic fibroblasts (MEFs) we demonstrate that coibamide-induced toxicity is delayed in ATG5-/- cells relative to ATG5+/+ cells. Time-dependent changes in annexin V staining, membrane integrity, metabolic capacity and caspase activation indicated that MEFs with a functional autophagy pathway are more sensitive to coibamide A. This pattern could be distinguished from autophagy modulators that induce acute ER stress (thapsigargin, tunicamycin), ATP depletion (oligomycin A) or mTORC1 inhibition (rapamycin), but was shared with the Sec61 inhibitor apratoxin A. Coibamide- or apratoxin-induced cell stress was further distinguished from the action of thapsigargin by a pattern of early LC3-II accumu...Continue Reading

References

Nov 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·E J BowmanK Altendorf
Oct 6, 1998·Nature·N MizushimaY Ohsumi
Dec 20, 2003·Cell Death and Differentiation·S Oyadomari, M Mori
Apr 8, 2004·Developmental Cell·Beth Levine, Daniel J Klionsky
Oct 7, 2004·Nature Cell Biology·Estela JacintoMichael N Hall
Nov 5, 2004·Nature·Akiko KumaNoboru Mizushima
Feb 14, 2006·Nature Chemical Biology·Hendrik LueschPeter G Schultz
Aug 12, 2006·The Journal of Biological Chemistry·Tomohiro YorimitsuDaniel J Klionsky
Sep 26, 2006·Nature Cell Biology·Shida YousefiHans-Uwe Simon
Oct 13, 2006·Molecular and Cellular Biology·Maiko OgataKazunori Imaizumi
Sep 25, 2007·Cell Cycle·Ezgi TasdemirGuido Kroemer
May 1, 2008·Journal of the American Chemical Society·Rebecca A MedinaKerry L McPhail
Jul 2, 2008·Nature Reviews. Drug Discovery·Edward M DriggersNicholas K Terrett
Oct 11, 2008·Cell Death and Differentiation·G KroemerUNKNOWN Nomenclature Committee on Cell Death 2009
Mar 13, 2009·Genes & Development·Andrew R J YoungMasashi Narita
Dec 15, 2011·Cold Spring Harbor Perspectives in Biology·Li Yen Mah, Kevin M Ryan
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
Feb 1, 2013·Nature·Sanae Shoji-KawataBeth Levine
Feb 5, 2013·Journal of Cell Science·Assaf D Rubinstein, Adi Kimchi
Apr 13, 2013·Current Topics in Medicinal Chemistry·Andrew T BockusR Scott Lokey
Sep 11, 2013·Journal of Natural Products·Christopher C ThornburgKerry L McPhail
Nov 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yang LiuBeth Levine
Jan 10, 2014·Nature Reviews. Molecular Cell Biology·Guillermo MariñoGuido Kroemer
Sep 23, 2014·Cell Death and Differentiation·L GalluzziG Kroemer
Sep 27, 2014·Cell Death and Differentiation·Y Liu, B Levine
Oct 22, 2014·Immunology and Cell Biology·Donna DentonSharad Kumar
Oct 24, 2014·Cell Death & Disease·H H LinD K Ann
Feb 6, 2015·The Journal of Clinical Investigation·Beth LevinePatrice Codogno

❮ Previous
Next ❯

Citations

Feb 19, 2020·Natural Product Reports·Hendrik Luesch, Ville O Paavilainen
Jan 15, 2020·Current Medicinal Chemistry·Dario MatuljaDean Marković
May 14, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lik Tong Tan, Ma Yadanar Phyo
Aug 2, 2018·Marine Drugs·Sergey A Dyshlovoy, Friedemann Honecker
Sep 25, 2020·Marine Drugs·Sergey A Dyshlovoy
Feb 17, 2021·Biochemical and Biophysical Research Communications·Wenli ShiHongchang Li
May 18, 2021·Organic & Biomolecular Chemistry·Oliver Andler, Uli Kazmaier
Sep 25, 2018·Journal of Medicinal Chemistry·Guiyang YaoLijing Fang

❮ Previous
Next ❯

Methods Mentioned

BETA
environmental stress
FACS

Software Mentioned

Graphpad Prism

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

ATG proteins

The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms