Oncogene, 2009-07, Vol.28 (28), p.2556-2568
2009
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- Autor(en) / Beteiligte
- Titel
- A novel role for MAP1 LC3 in nonautophagic cytoplasmic vacuolation death of cancer cells
- Ist Teil von
- Oncogene, 2009-07, Vol.28 (28), p.2556-2568
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2009
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Thiol reactive cyclopentenone prostaglandin, 15-deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ2), induced a novel, nonapoptotic and microtubule-associated protein 1 light chain 3 (MAP1 LC3) dependent but nonautophagic form of cell death in colon, breast and prostate cancer cell lines, characterized by extensive cytoplasmic vacuolation with dilatation of endoplasmic reticulum (ER). Disruption of sulfhydryl homeostasis, which resulted in ER stress, accumulation of ubiquitinated proteins and subsequent ER dilation, contributed to peroxisome proliferator-activated receptor γ (PPARγ)-independent cell death by 15d-PGJ2. Absence of intracellular organelles in these vacuoles, shown by electron microscopy and unique fragmentation of lamin B, suggested this form of cell death to be different from autophagy and apoptosis. Cell death induced by 15d-PGJ2 is prevented by cycloheximide and actinomycin D, suggesting a requirement of new protein synthesis for death with cytoplasmic vacuolation. Here, we report for the first time that upregulation and processing of autophagy marker LC3 is an important event in nonautophagic cytoplasmic vacuolation and cell death. Notably, knockdown of LC3 conferred significant protection against 15d-PGJ2-induced cytoplasmic vacuolation and cell death, suggesting a novel role of LC3 in a death process other than autophagy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/onc.2009.118Titel-ID: cdi_proquest_miscellaneous_67497465
- Format
- –
- Schlagworte
- Adaptor Proteins, Signal Transducing - genetics, Adaptor Proteins, Signal Transducing - physiology, Ageing, cell death, Antioxidants - pharmacology, Apoptosis, Autophagy, Autophagy-Related Protein 8 Family, Biological and medical sciences, Breast cancer, Cancer, Cancer cells, Cell Biology, Cell death, Cell Death - drug effects, Cell Death - physiology, Cell Line, Tumor, Cell physiology, Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes, Chemotherapy, Colon cancer, Control, Cycloheximide, Cytoplasm, Cytoplasm - metabolism, Electron microscopy, Endoplasmic reticulum, Endoplasmic Reticulum - metabolism, Fundamental and applied biological sciences. Psychology, Gene expression, Gene Knockdown Techniques, Genetic aspects, Health aspects, Homeostasis, Human Genetics, Humans, Internal Medicine, Medicine, Medicine & Public Health, Microfilament Proteins - genetics, Microfilament Proteins - physiology, Microtubule-associated protein 1, Microtubule-Associated Proteins - physiology, Molecular and cellular biology, Neoplasms - metabolism, Neoplasms - pathology, Oncology, Organelles, original-article, Peroxisome proliferator-activated receptors, PPAR gamma - physiology, Prostaglandin D2 - analogs & derivatives, Prostaglandin D2 - pharmacology, Prostate cancer, Protein biosynthesis, Protein synthesis, Reactive Oxygen Species - metabolism, Tumor cell lines, Ubiquitination, Up-Regulation, Vacuoles, Vacuoles - drug effects