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研究生： 錢舜益
Chien, Shun-Yi
論文名稱： 丙型干擾素誘導肺上皮惡性腫瘤進行一種類胞外捕捉性死亡
IFN-gamma induces a mimic extracellular trap cell death in lung epithelial maligancy
指導教授： 林秋烽
Lin, Chiou-Feng
學位類別： 碩士
Master
系所名稱： 醫學院 - 微生物及免疫學研究所
Department of Microbiology & Immunology
論文出版年： 2013
畢業學年度： 101
語文別： 英文
論文頁數： 70
中文關鍵詞： 丙型干擾素 、細胞自噬作用 、組蛋白瓜胺酸化 、胞外捕捉性死亡 、肺癌
外文關鍵詞： IFN-γ, autophagy, hitone H3 citrullination, ETosis, lung cancer
相關次數： 點閱：113  下載：1 
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    • 丙型干擾素藉由細胞自噬作用來促進其訊息傳遞和生物功能包括發炎、抑菌以及抗癌。本篇研究著重探討細胞自噬作用對於丙型干擾素誘導細胞毒性的角色。丙型干擾素會造成肺癌細胞株A549生長抑制並產生細胞毒性。丙型干擾素不會造成細胞週期停滯卻誘導細胞凋亡的現象包括染色體的凝聚和磷脂醯絲胺酸胞外暴露，同時伴隨著細胞毒性相關的類細胞壞死現象。藉由細胞核的染色、體外核小體的偵測、電子顯微鏡觀察以及核纖層蛋白染色顯示丙型干擾素誘導類胞外捕捉性死亡，且這樣的現象是由caspase蛋白所調控。研究證實IRGM1以及ATF6蛋白調控細胞自噬作用進而促進丙型干擾素誘導細胞毒性、caspase-3蛋白的活化以及類胞外捕捉性死亡現象。由丙型干擾素誘導的NADPH氧化酶表現及下游活性氧化物會促使染色體損害進而促進類胞外捕捉性死亡。處理丙型干擾素會使得FADD蛋白會和細胞自噬體結合，顯示細胞自噬作用會誘導FADD蛋白調控caspase-3活化。在細胞自噬作用和caspase活化之後，丙型干擾素導致染色體損害並伴隨著ATR/ATM蛋白調控的類胞外捕捉性死亡以及細胞毒性產生。另外，丙型干擾素誘導的胞外捕捉性死亡取決於PAD4蛋白調控的組蛋白瓜胺酸化，而調控PAD4蛋白活化的機制包括染色體損害相關的ATR/ATM及NADPH氧化酶與內質網壓力相關的ATF6及鈣離子訊號。重要的是，生長抑制、細胞毒性、caspase-3蛋白活化、染色體損害以及類胞外捕捉性死亡在細胞自噬作用缺乏和具丙型干擾素抗性的肺癌細胞株PC14PE6/AS2無法產生。這些結果證實細胞自噬作用存在下，丙型干擾素誘導caspase調控的染色體損害伴隨著PAD4調控組蛋白瓜胺酸化的胞外捕捉性死亡現象，並提供新穎的丙型干擾素細胞毒性證據。

    Interferon (IFN)-γ causes autophagy to facilitate signaling and bioactivities, including inflammation, anti-microbe, and anticancer. This study aims to investigate the role of autophagy in cytotoxicity of IFN-γ. IFN-γ induces growth inhibition and cytotoxicity in A549 human lung cancer cells. Without cell cycle arrest, the presence of apoptotic events, such as DNA condensation/fragmentation and phosphatidylserine externalization, accompanied by necrosis-like cell death was related to IFN-γ cytotoxicity. Surprisingly, nuclear staining, extracellular nucleosome detection, electronic microscopic observation, and lamin staining showed a mimic extracellular trap cell death (ETosis) caused by IFN-γ and regulated by caspases. Autophagy regulated by immunity-related GTPase family M protein (IRGM) 1 and activating transcription factor (ATF) 6 facilitated IFN-γ-induced cytotoxicity, caspase activation, and ETosis. Nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase-associated reactive oxygen species (ROS) generation also promoted Fas-associated protein with death domain (FADD) was co-localized with microtubule-associated protein 1 light chian (LC) 3 punctas under IFN-γ treatment, indicating that autophagy activates FADD-mediated caspase activation. Following autophagy and caspase activation, IFN-γ resulted in DNA damage followed by ataxia telangiectasia and Rad3-related protein (ATR)/ataxia-telangiectasia mutated (ATM)- and NADPH oxidase-regulated ETosis and cytotoxicity independent of p53. Moreover, IFN-γ-induced ETosis was depended on peptidyl arginine deiminase (PAD) 4-mediated histone 3 citrullination while the regulation of PAD4 was regulated by DNA damage-associated ATR/ATM and NADPH oxidase and endoplasmic reticulum stress-associated ATF6 and calcium signaling. Notably, growth inhibition, cytotoxicity, caspase-3 activation, DNA damage, and ETosis were defect in PC14PE6/AS2 human lung cancer cells while the cells showed autophagy insusceptibility as well as IFN-γ resistance. These results provide the novel evidence to demonstrate that, under autophagy, IFN-γ triggers caspase-mediated DNA damage-associated a mimic ETosis accompanied by PAD4-mediated H3 citrullination for cytotoxicity.

    Abstract in Chinese I Abstract in English II Acknowledgement III Abbreviations IV Contents VIII I. Introduction 1 I-1. Interferon (IFN)-γ 1 I-2. The Role of IFN-γ in Cancer 1 I-3. Autophagy 2 I-4. The Role of Autophagy in Cancer 3 I-5. Autophagy Induction by IFN-γ 4 I-6. Extracellular Traps Cell Death (ETosis) 4 I-7. The Regulation of ETosis 5 II. Objective and Specific Aims 7 Specific Aim 1: To clarify the effects of IFN-γ on lung epithelial malignancy. 7 Specific Aim 2: To investigate the role of autophagy in IFN-γ-induced cell death. 7 Specific Aim 3: To verify the mechanisms of IFN-γ-induced autophagy-related cell death. 7 III. Materials and Methods 8 III-1. Cells and Cell Culture 8 III-2. Reagents and Antibodies 8 III-3. Proliferation Assay 9 III-4. Cytotoxicity Assay 9 III-5. Cell Cycle and Cell Death Analysis 9 III-6. Western Blot Analysis 10 III-7. Immunostaining 10 III-8. Enzyme-linked Immunosorbent Assay 11 III-9. Lentiviral-based RNA Interference Transfection 11 III-10. Luciferase Reporter Assay 12 III-10. Transmission Electron Microscopy 12 III-11. Determination of ROS Generation 13 III-12. Determination of Calcium Release 13 III-13. Live Cell Imaging 13 III-13. Statistical Analysis 14 IV. Results 15 IV-1. IFN-γ Induces Cell Proliferation Inhibition and Cytotoxicity in Lung Epithelial Cancer Cell A549 Accompanied by Apoptosis and Non-apoptotic Cell Death 15 IV-2. Cell Death Caused by IFN-γ, which Regulated by Caspase-3, is Characterized as a Mimic ETosis 15 IV-3. Autophagy and ROS are Required for IFN-γ-induced a Mimic ETosis 17 IV-4. IFN-γ Induces IRF-1-regulated but CD95-independent Caspase-8/Caspase-3 Activation and a Mimic ETosis through Atg5/FADD-regulated Manner 18 IV-5. IFN-γ Induces Caspase-3-regulated DNA Damage Followed by ATR/ATM-associated a Mimic ETosis 19 IV-6. ATR/ATM Regulates PAD4 Activation While PAD4-mediated Histone H3 Hypercitrullination Is Required for IFN-γ-induced a Mimic ETosis 20 IV-7. Autophagy Resistant PC14PE6/AS2 Lung Cancer Cells Are Resistant to IFN-γ Response 21 V. Discussion 22 VI. Conclusion and Implication 28 References 29 Table 38 Figures and Figure Legends 40 Figure 1. Exogenous IFN-γ causes cell proliferation inhibition and cytotoxicity accompanied by concurrent apoptosis as well as non-apoptotic cell death. 40 Figure 3. Nuclear staining, extracellular nucleosome detection, nuclear lamin A/C staining, and electronic microscopic observation, which characterized with vacuolization, autophagy, chromatin de-condensation, nuclear membrane destruction, show a mimic to ETosis that is unusually regulated by caspase-3. 43 Figure 4. Gene silence in A549 cells used in this study. 45 Figure 5. Autophagy, IRGM1, and ATF6 dependently, facilitates IFN-γ-induced cytotoxic ETosis. 46 Figure 6. IFN-γ causes ROS generation and NADPH oxidase expression followed by ETosis. 48 Figure 7. An IRF1-regulated non-CD95-mediated caspase-8/ caspase-3 signaling axis following Atg5/FADD/caspase-8 interaction around autophagosomes is required for ETosis. 49 Figure 8. IFN-γ results in DNA damage followed by ATR/ATM- but not p53-regulated ETosis. 51 Figure 9. ATR/ATM acts upstream of PAD4-mediated histone 3 hyper- citrullination and ETosis. 53 Figure 10. ETosis is defect in cells which are originally presenting IFN-γ and autophagy resistance. 55 Figure 11. Schematic model for the molecular mechanisms of IFN-γ in regulating a mimic ETosis in lung epithelial malignancy. 57 Appendix 58 A. Figures 58 B. Materials 59 B-1 Chemicals 59 B-2 Antibodies 60 B-3 Kits 62 B-4 Consumables 62 B-5 Apparatus 62 C. Methods 63 C-1 Cell culture 63 C-2 Western blot 65 C-3 Lentiviral-based shRNA knockdown 67 C-4 PI staining 68 C-5 Intracellular ROS assay 69 C-6 Intracellular calcium assay 69 CURRICULUM VITAE 70

    Aita, V. M., X. H. Liang, V. V. Murty, D. L. Pincus, W. Yu, E. Cayanis, S. Kalachikov, T. C. Gilliam & B. Levine (1999) Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. Genomics, 59, 59-65.
    Apel, A., H. Zentgraf, M. W. Buchler & I. Herr (2009) Autophagy-A double-edged sword in oncology. Int J Cancer, 125, 991-5.
    Bedard, K. & K. H. Krause (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev, 87, 245-313.
    Bell, B. D., S. Leverrier, B. M. Weist, R. H. Newton, A. F. Arechiga, K. A. Luhrs, N. S. Morrissette & C. M. Walsh (2008) FADD and caspase-8 control the outcome of autophagic signaling in proliferating T cells. Proc Natl Acad Sci U S A, 105, 16677-82.
    Burke, B. & J. Ellenberg (2002) Remodelling the walls of the nucleus. Nat Rev Mol Cell Biol, 3, 487-97.
    Bursch, W., K. Hochegger, L. Torok, B. Marian, A. Ellinger & R. S. Hermann (2000) Autophagic and apoptotic types of programmed cell death exhibit different fates of cytoskeletal filaments. J Cell Sci, 113 ( Pt 7), 1189-98.
    Cassatella, M. A., F. Bazzoni, R. M. Flynn, S. Dusi, G. Trinchieri & F. Rossi (1990) Molecular basis of interferon-gamma and lipopolysaccharide enhancement of phagocyte respiratory burst capability. Studies on the gene expression of several NADPH oxidase components. J Biol Chem, 265, 20241-6.
    Chang, C. P., M. C. Yang & H. Y. Lei (2011) Concanavalin A/IFN-gamma triggers autophagy-related necrotic hepatocyte death through IRGM1-mediated lysosomal membrane disruption. PLoS One, 6, e28323.
    Chang, Y. P., C. C. Tsai, W. C. Huang, C. Y. Wang, C. L. Chen, Y. S. Lin, J. I. Kai, C. Y. Hsieh, Y. L. Cheng, P. C. Choi, S. H. Chen, S. P. Chang, H. S. Liu & C. F. Lin (2010) Autophagy facilitates IFN-gamma-induced Jak2-STAT1 activation and cellular inflammation. J Biol Chem, 285, 28715-22.
    Chen, H. Y. & E. White (2011) Role of autophagy in cancer prevention. Cancer Prev Res (Phila), 4, 973-83.
    Decker, T., S. Stockinger, M. Karaghiosoff, M. Muller & P. Kovarik (2002) IFNs and STATs in innate immunity to microorganisms. J Clin Invest, 109, 1271-7.
    Desai, S., Z. Liu, J. Yao, N. Patel, J. Chen, Y. Wu, E. E. Ahn, O. Fodstad & M. Tan (2013) Heat shock factor 1 (HSF1) controls chemoresistance and autophagy through transcriptional regulation of autophagy-related protein 7 (ATG7). J Biol Chem, 288, 9165-76.
    Eklund, E. A. & R. Kakar (1999) Recruitment of CREB-binding protein by PU.1, IFN-regulatory factor-1, and the IFN consensus sequence-binding protein is necessary for IFN-gamma-induced p67phox and gp91phox expression. J Immunol, 163, 6095-105.
    Fuchs, T. A., U. Abed, C. Goosmann, R. Hurwitz, I. Schulze, V. Wahn, Y. Weinrauch, V. Brinkmann & A. Zychlinsky (2007) Novel cell death program leads to neutrophil extracellular traps. J Cell Biol, 176, 231-41.
    Gade, P., G. Ramachandran, U. B. Maachani, M. A. Rizzo, T. Okada, R. Prywes, A. S. Cross, K. Mori & D. V. Kalvakolanu (2012) An IFN-gamma-stimulated ATF6-C/EBP-beta-signaling pathway critical for the expression of Death Associated Protein Kinase 1 and induction of autophagy. Proc Natl Acad Sci U S A, 109, 10316-21.
    Gozuacik, D. & A. Kimchi (2004) Autophagy as a cell death and tumor suppressor mechanism. Oncogene, 23, 2891-906.
    Guachalla, L. M. & K. L. Rudolph (2010) ROS induced DNA damage and checkpoint responses: influences on aging? Cell Cycle, 9, 4058-60.
    Guimaraes-Costa, A. B., M. T. Nascimento, A. B. Wardini, L. H. Pinto-da-Silva & E. M. Saraiva (2012) ETosis: A Microbicidal Mechanism beyond Cell Death. J Parasitol Res, 2012, 929743.
    Gupta, A. K., M. B. Joshi, M. Philippova, P. Erne, P. Hasler, S. Hahn & T. J. Resink (2010) Activated endothelial cells induce neutrophil extracellular traps and are susceptible to NETosis-mediated cell death. FEBS Lett, 584, 3193-7.
    Gupta, J. W., M. Kubin, L. Hartman, M. Cassatella & G. Trinchieri (1992) Induction of expression of genes encoding components of the respiratory burst oxidase during differentiation of human myeloid cell lines induced by tumor necrosis factor and gamma-interferon. Cancer Res, 52, 2530-7.
    Gutierrez, M. G., S. S. Master, S. B. Singh, G. A. Taylor, M. I. Colombo & V. Deretic (2004) Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell, 119, 753-66.
    Harris, J. (2011) Autophagy and cytokines. Cytokine, 56, 140-4.
    Harris, J., S. S. Master, S. A. De Haro, M. Delgado, E. A. Roberts, J. C. Hope, J. Keane & V. Deretic (2009) Th1-Th2 polarisation and autophagy in the control of intracellular mycobacteria by macrophages. Vet Immunol Immunopathol, 128, 37-43.
    Harvat, B. L., P. Seth & A. M. Jetten (1997) The role of p27Kip1 in gamma interferon-mediated growth arrest of mammary epithelial cells and related defects in mammary carcinoma cells. Oncogene, 14, 2111-22.
    He, C. & B. Levine (2010) The Beclin 1 interactome. Curr Opin Cell Biol, 22, 140-9.
    Ikeda, H., L. J. Old & R. D. Schreiber (2002) The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev, 13, 95-109.
    Kabeya, Y., N. Mizushima, T. Ueno, A. Yamamoto, T. Kirisako, T. Noda, E. Kominami, Y. Ohsumi & T. Yoshimori (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J, 19, 5720-8.
    Kaplan, D. H., V. Shankaran, A. S. Dighe, E. Stockert, M. Aguet, L. J. Old & R. D. Schreiber (1998) Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci U S A, 95, 7556-61.
    Karantza-Wadsworth, V., S. Patel, O. Kravchuk, G. Chen, R. Mathew, S. Jin & E. White (2007) Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev, 21, 1621-35.
    Kimmelman, A. C. (2011) The dynamic nature of autophagy in cancer. Genes Dev, 25, 1999-2010.
    Kivinen, K., M. Kallajoki & P. Taimen (2005) Caspase-3 is required in the apoptotic disintegration of the nuclear matrix. Exp Cell Res, 311, 62-73.
    Kominsky, S., H. M. Johnson, G. Bryan, T. Tanabe, A. C. Hobeika, P. S. Subramaniam & B. Torres (1998) IFNgamma inhibition of cell growth in glioblastomas correlates with increased levels of the cyclin dependent kinase inhibitor p21WAF1/CIP1. Oncogene, 17, 2973-9.
    Kroemer, G., G. Marino & B. Levine (2010) Autophagy and the integrated stress response. Mol Cell, 40, 280-93.
    Kumatori, A., D. Yang, S. Suzuki & M. Nakamura (2002) Cooperation of STAT-1 and IRF-1 in interferon-gamma-induced transcription of the gp91(phox) gene. J Biol Chem, 277, 9103-11.
    Lees-Miller, S. P. (2006) Dysfunction of lamin A triggers a DNA damage response and cellular senescence. DNA Repair (Amst), 5, 286-9.
    Levine, B. & G. Kroemer (2008) Autophagy in the pathogenesis of disease. Cell, 132, 27-42.
    Levine, B., N. Mizushima & H. W. Virgin (2011) Autophagy in immunity and inflammation. Nature, 469, 323-35.
    Li, P., Q. Du, Z. Cao, Z. Guo, J. Evankovich, W. Yan, Y. Chang, L. Shao, D. B. Stolz, A. Tsung & D. A. Geller (2012) Interferon-gamma induces autophagy with growth inhibition and cell death in human hepatocellular carcinoma (HCC) cells through interferon-regulatory factor-1 (IRF-1). Cancer Lett, 314, 213-22.
    Li, P., M. Li, M. R. Lindberg, M. J. Kennett, N. Xiong & Y. Wang (2010) PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med, 207, 1853-62.
    Lin, W., P. E. Kunkler, H. P. Harding, D. Ron, R. P. Kraig & B. Popko (2008) Enhanced integrated stress response promotes myelinating oligodendrocyte survival in response to interferon-gamma. Am J Pathol, 173, 1508-17.
    Lobrich, M. & P. A. Jeggo (2007) The impact of a negligent G2/M checkpoint on genomic instability and cancer induction. Nat Rev Cancer, 7, 861-9.
    Luth, S., J. Schrader, S. Zander, A. Carambia, J. Buchkremer, S. Huber, K. Reifenberg, K. Yamamura, P. Schirmacher, A. W. Lohse & J. Herkel (2011) Chronic inflammatory IFN-gamma signaling suppresses hepatocarcinogenesis in mice by sensitizing hepatocytes for apoptosis. Cancer Res, 71, 3763-71.
    Martinelli, S., M. Urosevic, A. Daryadel, P. A. Oberholzer, C. Baumann, M. F. Fey, R. Dummer, H. U. Simon & S. Yousefi (2004) Induction of genes mediating interferon-dependent extracellular trap formation during neutrophil differentiation. J Biol Chem, 279, 44123-32.
    Mathew, R., V. Karantza-Wadsworth & E. White (2007a) Role of autophagy in cancer. Nat Rev Cancer, 7, 961-7.
    Mathew, R., S. Kongara, B. Beaudoin, C. M. Karp, K. Bray, K. Degenhardt, G. Chen, S. Jin & E. White (2007b) Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev, 21, 1367-81.
    Matsuzawa, T., B. H. Kim, A. R. Shenoy, S. Kamitani, M. Miyake & J. D. Macmicking (2012) IFN-gamma elicits macrophage autophagy via the p38 MAPK signaling pathway. J Immunol, 189, 813-8.
    Mizushima, N., H. Sugita, T. Yoshimori & Y. Ohsumi (1998) A new protein conjugation system in human. The counterpart of the yeast Apg12p conjugation system essential for autophagy. J Biol Chem, 273, 33889-92.
    Neeli, I., N. Dwivedi, S. Khan & M. Radic (2009) Regulation of extracellular chromatin release from neutrophils. J Innate Immun, 1, 194-201.
    Neeli, I., S. N. Khan & M. Radic (2008) Histone deimination as a response to inflammatory stimuli in neutrophils. J Immunol, 180, 1895-902.
    Park, H. J., S. J. Lee, S. H. Kim, J. Han, J. Bae, S. J. Kim, C. G. Park & T. Chun (2011) IL-10 inhibits the starvation induced autophagy in macrophages via class I phosphatidylinositol 3-kinase (PI3K) pathway. Mol Immunol, 48, 720-7.
    Platanias, L. C. (2005) Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol, 5, 375-86.
    Podhorecka, M., A. Skladanowski & P. Bozko (2010) H2AX Phosphorylation: Its Role in DNA Damage Response and Cancer Therapy. J Nucleic Acids, 2010.
    Putney, J. W., Jr. & C. M. Ribeiro (2000) Signaling pathways between the plasma membrane and endoplasmic reticulum calcium stores. Cell Mol Life Sci, 57, 1272-86.
    Pyo, J. O., M. H. Jang, Y. K. Kwon, H. J. Lee, J. I. Jun, H. N. Woo, D. H. Cho, B. Choi, H. Lee, J. H. Kim, N. Mizushima, Y. Oshumi & Y. K. Jung (2005) Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J Biol Chem, 280, 20722-9.
    Remijsen, Q., T. W. Kuijpers, E. Wirawan, S. Lippens, P. Vandenabeele & T. Vanden Berghe (2011a) Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality. Cell Death Differ, 18, 581-8.
    Remijsen, Q., T. Vanden Berghe, E. Wirawan, B. Asselbergh, E. Parthoens, R. De Rycke, S. Noppen, M. Delforge, J. Willems & P. Vandenabeele (2011b) Neutrophil extracellular trap cell death requires both autophagy and superoxide generation. Cell Res, 21, 290-304.
    Rohrbach, A. S., D. J. Slade, P. R. Thompson & K. A. Mowen (2012) Activation of PAD4 in NET formation. Front Immunol, 3, 360.
    Scherz-Shouval, R. & Z. Elazar (2011) Regulation of autophagy by ROS: physiology and pathology. Trends Biochem Sci, 36, 30-8.
    Scherz-Shouval, R., E. Shvets, E. Fass, H. Shorer, L. Gil & Z. Elazar (2007) Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J, 26, 1749-60.
    Schmitt, M. J., D. Philippidou, S. E. Reinsbach, C. Margue, A. Wienecke-Baldacchino, D. Nashan, I. Behrmann & S. Kreis (2012) Interferon-gamma-induced activation of Signal Transducer and Activator of Transcription 1 (STAT1) up-regulates the tumor suppressing microRNA-29 family in melanoma cells. Cell Commun Signal, 10, 41.
    Schroder, K., P. J. Hertzog, T. Ravasi & D. A. Hume (2004) Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol, 75, 163-89.
    Shuai, K. & B. Liu (2003) Regulation of JAK-STAT signalling in the immune system. Nat Rev Immunol, 3, 900-11.
    Singh, S. B., A. S. Davis, G. A. Taylor & V. Deretic (2006) Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science, 313, 1438-41.
    Sirichanchuen, B., T. Pengsuparp & P. Chanvorachote (2012) Long-term cisplatin exposure impairs autophagy and causes cisplatin resistance in human lung cancer cells. Mol Cell Biochem, 364, 11-8.
    Song, J., Z. Qu, X. Guo, Q. Zhao, X. Zhao, L. Gao, K. Sun, F. Shen, M. Wu & L. Wei (2009) Hypoxia-induced autophagy contributes to the chemoresistance of hepatocellular carcinoma cells. Autophagy, 5, 1131-44.
    Song, M. M. & K. Shuai (1998) The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities. J Biol Chem, 273, 35056-62.
    Stang, M. T., M. J. Armstrong, G. A. Watson, K. Y. Sung, Y. Liu, B. Ren & J. H. Yim (2007) Interferon regulatory factor-1-induced apoptosis mediated by a ligand-independent fas-associated death domain pathway in breast cancer cells. Oncogene, 26, 6420-30.
    Street, S. E., J. A. Trapani, D. MacGregor & M. J. Smyth (2002) Suppression of lymphoma and epithelial malignancies effected by interferon gamma. J Exp Med, 196, 129-34.
    Tanikawa, C., M. Espinosa, A. Suzuki, K. Masuda, K. Yamamoto, E. Tsuchiya, K. Ueda, Y. Daigo, Y. Nakamura & K. Matsuda (2012) Regulation of histone modification and chromatin structure by the p53-PADI4 pathway. Nat Commun, 3, 676.
    Tanikawa, C., K. Ueda, H. Nakagawa, N. Yoshida, Y. Nakamura & K. Matsuda (2009) Regulation of protein Citrullination through p53/PADI4 network in DNA damage response. Cancer Res, 69, 8761-9.
    Thapa, R. J., S. H. Basagoudanavar, S. Nogusa, K. Irrinki, K. Mallilankaraman, M. J. Slifker, A. A. Beg, M. Madesh & S. Balachandran (2011) NF-kappaB protects cells from gamma interferon-induced RIP1-dependent necroptosis. Mol Cell Biol, 31, 2934-46.
    Tooze, S. A. & T. Yoshimori (2010) The origin of the autophagosomal membrane. Nat Cell Biol, 12, 831-5.
    Tsai, C. C., J. I. Kai, W. C. Huang, C. Y. Wang, Y. Wang, C. L. Chen, Y. T. Fang, Y. S. Lin, R. Anderson, S. H. Chen, C. W. Tsao & C. F. Lin (2009) Glycogen synthase kinase-3beta facilitates IFN-gamma-induced STAT1 activation by regulating Src homology-2 domain-containing phosphatase 2. J Immunol, 183, 856-64.
    Tu, S. P., M. Quante, G. Bhagat, S. Takaishi, G. Cui, X. D. Yang, S. Muthuplani, W. Shibata, J. G. Fox, D. M. Pritchard & T. C. Wang (2011) IFN-gamma inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T-cell apoptosis. Cancer Res, 71, 4247-59.
    Urban, C. F., D. Ermert, M. Schmid, U. Abu-Abed, C. Goosmann, W. Nacken, V. Brinkmann, P. R. Jungblut & A. Zychlinsky (2009) Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog, 5, e1000639.
    Wang, C. Y., T. H. Chiang, C. L. Chen, P. C. Tseng, S. Y. Chien, Y. J. Chuang, T. T. Yang, C. Y. Hsieh, P. C. Choi & C. F. Lin (2013) Autophagy facilitates cytokine-induced ICAM-1 expression. Innate Immun.
    Wang, Y., M. Li, S. Stadler, S. Correll, P. Li, D. Wang, R. Hayama, L. Leonelli, H. Han, S. A. Grigoryev, C. D. Allis & S. A. Coonrod (2009) Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J Cell Biol, 184, 205-13.
    Wang, Y., J. Wysocka, J. Sayegh, Y. H. Lee, J. R. Perlin, L. Leonelli, L. S. Sonbuchner, C. H. McDonald, R. G. Cook, Y. Dou, R. G. Roeder, S. Clarke, M. R. Stallcup, C. D. Allis & S. A. Coonrod (2004) Human PAD4 regulates histone arginine methylation levels via demethylimination. Science, 306, 279-83.
    Watanabe, Y., O. Suzuki, T. Haruyama & T. Akaike (2003) Interferon-gamma induces reactive oxygen species and endoplasmic reticulum stress at the hepatic apoptosis. J Cell Biochem, 89, 244-53.
    White, E. & R. S. DiPaola (2009) The double-edged sword of autophagy modulation in cancer. Clin Cancer Res, 15, 5308-16.
    Wu, S., X. Wang, J. Chen & Y. Chen (2013) Autophagy of cancer stem cells is involved with chemoresistance of colon cancer cells. Biochem Biophys Res Commun, 434, 898-903.
    Xu, N., J. Zhang, C. Shen, Y. Luo, L. Xia, F. Xue & Q. Xia (2012) Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. Biochem Biophys Res Commun, 423, 826-31.
    Xu, X., X. Y. Fu, J. Plate & A. S. Chong (1998) IFN-gamma induces cell growth inhibition by Fas-mediated apoptosis: requirement of STAT1 protein for up-regulation of Fas and FasL expression. Cancer Res, 58, 2832-7.
    Yang, D., S. G. Elner, Z. M. Bian, G. O. Till, H. R. Petty & V. M. Elner (2007) Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells. Exp Eye Res, 85, 462-72.
    Yang, L., Y. Yu, R. Kang, M. Yang, M. Xie, Z. Wang, D. Tang, M. Zhao, L. Liu, H. Zhang & L. Cao (2012) Up-regulated autophagy by endogenous high mobility group box-1 promotes chemoresistance in leukemia cells. Leuk Lymphoma, 53, 315-22.
    Yang, Z. & D. J. Klionsky (2010) Eaten alive: a history of macroautophagy. Nat Cell Biol, 12, 814-22.
    Young, M. M., Y. Takahashi, O. Khan, S. Park, T. Hori, J. Yun, A. K. Sharma, S. Amin, C. D. Hu, J. Zhang, M. Kester & H. G. Wang (2012) Autophagosomal membrane serves as platform for intracellular death-inducing signaling complex (iDISC)-mediated caspase-8 activation and apoptosis. J Biol Chem, 287, 12455-68.
    Zhang, J. G., A. Farley, S. E. Nicholson, T. A. Willson, L. M. Zugaro, R. J. Simpson, R. L. Moritz, D. Cary, R. Richardson, G. Hausmann, B. J. Kile, S. B. Kent, W. S. Alexander, D. Metcalf, D. J. Hilton, N. A. Nicola & M. Baca (1999) The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation. Proc Natl Acad Sci U S A, 96, 2071-6.

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