Regulation of the Death-Associated Protein Kinase 1 Expression and Autophagy via ATF6 Requires Apoptosis Signal-Regulating Kinase 1

Gade, Padmaja; Manjegowda, Srikanta B.; Nallar, Shreeram C.; Maachani, Uday B.; Cross, Alan S.; Kalvakolanu, Dhananjaya V.

doi:10.1128/mcb.00397-14

Cited by 68 publications

(66 citation statements)

References 52 publications

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“…The transcription factor C/EBP-β regulates transcription of DAPK1 in response to IFN-γ, in collaboration with ATF6, a key ER stress-activated transcription factor (Gade et al., 2012, Gade et al., 2014, Kalvakolanu and Gade, 2012). ER stress causes dissociation of ATF6 from its inhibitor, allowing its translocation from the ER membrane to the Golgi apparatus, where site-specific endoproteolysis generates transcriptionally active ATF6, permitting its nuclear entry and target gene regulation (Shen and Prywes, 2005).…”

Section: Resultsmentioning

confidence: 99%

Noncanonical Fungal Autophagy Inhibits Inflammation in Response to IFN-γ via DAPK1

Oikonomou

Moretti

Renga

et al. 2016

Cell Host & Microbe

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SummaryDefects in a form of noncanonical autophagy, known as LC3-associated phagocytosis (LAP), lead to increased inflammatory pathology during fungal infection. Although LAP contributes to fungal degradation, the molecular mechanisms underlying LAP-mediated modulation of inflammation are unknown. We describe a mechanism by which inflammation is regulated during LAP through the death-associated protein kinase 1 (DAPK1). The ATF6/C/EBP-β/DAPK1 axis activated by IFN-γ not only mediates LAP to Aspergillus fumigatus but also concomitantly inhibits Nod-like receptor protein 3 (NLRP3) activation and restrains pathogenic inflammation. In mouse models and patient samples of chronic granulomatous disease, which exhibit defective autophagy and increased inflammasome activity, IFN-γ restores reduced DAPK1 activity and dampens fungal growth. Additionally, in a cohort of hematopoietic stem cell-transplanted patients, a genetic DAPK1 deficiency is associated with increased inflammation and heightened aspergillosis susceptibility. Thus, DAPK1 is a potential drugable player in regulating the inflammatory response during fungal clearance initiated by IFN-γ.

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Section: Resultsmentioning

confidence: 99%

Noncanonical Fungal Autophagy Inhibits Inflammation in Response to IFN-γ via DAPK1

Oikonomou

Moretti

Renga

et al. 2016

Cell Host & Microbe

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“…The transcriptional activity of ATF6 is also determined by its binding to different cofactors and transcription factors, including NF-Y/CBF, YY1, and TATA-binding protein (TBP; refs. 25 , 69 , 70 ) and by phosphorylation ( 71 ). XBP1s is regulated by acetylation and sumoylation, in addition to phosphorylation through p38 (72)(73)(74).…”

Section: Upr Transcription Factor Networkmentioning

confidence: 99%

Endoplasmic Reticulum Stress–Activated Cell Reprogramming in Oncogenesis

2015

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Stress induced by the accumulation of unfolded proteins in the endoplasmic reticulum (ER) is observed in many human diseases, including cancers. Cellular adaptation to ER stress is mediated by the unfolded protein response (UPR), which aims at restoring ER homeostasis. The UPR has emerged as a major pathway in remodeling cancer gene expression, thereby either preventing cell transformation or providing an advantage to transformed cells. UPR sensors are highly regulated by the formation of dynamic protein scaffolds, leading to integrated reprogramming of the cells. Herein, we describe the regulatory mechanisms underlying UPR signaling upon cell intrinsic or extrinsic challenges, and how they engage cell transformation programs and/or provide advantages to cancer cells, leading to enhanced aggressiveness or chemoresistance. We discuss the emerging crosstalk between the UPR and related metabolic processes to ensure maintenance of protein homeostasis and its impact on cell transformation and tumor growth.Signifi cance: ER stress signaling is dysregulated in many forms of cancer and contributes to tumor growth as a survival factor, in addition to modulating other disease-associated processes, including cell migration, cell transformation, and angiogenesis. Evidence for targeting the ER stress signaling pathway as an anticancer strategy is compelling, and novel agents that selectively inhibit the UPR have demonstrated preliminary evidence of preclinical effi cacy with an acceptable safety profi le. Cancer Discov; 5(6);

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“…Death associated protein kinase 1 (DAPK1) has an important role in cell death and regulation of autophagy. It is known that DAPK1 has tumor suppressor role [47]. When the expression of DAPK1 increased in cell, the numbers of LCШ, markers of autophagy, increased was observed.…”

Section: Autophagy and Basal Cell Carcinomamentioning

confidence: 94%

“…When the expression of DAPK1 increased in cell, the numbers of LCШ, markers of autophagy, increased was observed. DAPK1 were actually identified as activators of IFNG [47,48].…”

Section: Autophagy and Basal Cell Carcinomamentioning

confidence: 99%

The Role of Autophagy in Stress and Cancer

Bostancıklıoğlu¹

2015

Single Cell Biol

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Programmed cell death plays an important role in development and disease. There are three main types of programmed cell death: apoptosis, autophagy, and necrosis. Apoptosis works on the two basic pathways called extrinsic and intrinsic; when there is a stress factor in a cell, apoptosis starts. Autophagy is critical for the continuation of normal human physiology such as the cellular homeostasis, energy balance, development and cellular defense. In addition to these, it may play a role in the pathogenesis of cancer, neurodegenerative diseases, aging, muscular diseases, infectious diseases, and immune system diseases.While some autophagy genes showed tumor suppressive effect during the development of cancer, some other genes contributes to the survival of cancer cells during cancer progression. Therefore, the relationship between autophagy and cancer is quite complex. The role of autophagy in cancer varies depending on the stage of the cancer, the metabolic status of cell and the presence of stress. Also, it was reported that the expression of certain molecules associated with autophagy vary in different types of cancer. Autophagy is activated and allows the continuation of the viability of tumor cells in hypoxia. In case of nutrient deficiency, autophagy allows tumor tissue to gain time until nutrient, oxygen and growth factors become eligible again. Therefore, autophagy is seen as a necessary mechanism for tumor continuity. Autophagy increases both in cancer cells and normal cells during the cancer treatment. But, due to cancer cells use autophagy to survive more than normal cells; this case may generate new therapeutic opportunities. The studies needed to conduct to find new ways for using the genes play role in autophagy in cancer treatment.In the present study, we aimed to throw light on the interaction of autophagy mechanism and some stresses such as ischemia and reperfusion and cancer development.

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Regulation of the Death-Associated Protein Kinase 1 Expression and Autophagy via ATF6 Requires Apoptosis Signal-Regulating Kinase 1

Cited by 68 publications

References 52 publications

Noncanonical Fungal Autophagy Inhibits Inflammation in Response to IFN-γ via DAPK1

Noncanonical Fungal Autophagy Inhibits Inflammation in Response to IFN-γ via DAPK1

Endoplasmic Reticulum Stress–Activated Cell Reprogramming in Oncogenesis

The Role of Autophagy in Stress and Cancer

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