Regulation of an
            <i>ATG7</i>
            -
            <i>beclin 1</i>
            Program of Autophagic Cell Death by Caspase-8

Yu, Li; Alva, Ajjai; Su, Helen C.; Dutt, Parmesh; Freundt, Eric C.; Welsh, Sarah J.; Baehrecke, Eric H.; Lenardo, Michael J.

doi:10.1126/science.1096645

Cited by 1,192 publications

(1,076 citation statements)

References 25 publications

Supporting

Mentioning

997

Contrasting

Unclassified

Order By: Relevance

“…102,104 Some findings suggest that prolonged stimulation of autophagy may be detrimental to cancer cells and that therapies that inhibit autophagy may lead to enhanced tumor growth. 105 Other studies, however, support the use of autophagy inhibitors as potentiators of anticancer agents. 106,107 As an example, the mammalian target of rapamycin (mTOR) kinase inhibitor everolimus, which induces autophagy, prolonged the survival of patients affected by renal cell carcinoma in a phase-III clinical trial.…”

Section: Effects On Tumor Cells and On Tumor Microenvironmentmentioning

confidence: 99%

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

et al. 2013

View full text Add to dashboard Cite

Conventional anticancer chemotherapy has been historically thought to act through direct killing of tumor cells. This concept stems from the fact that cytotoxic drugs interfere with DNA synthesis and replication. Accumulating evidence, however, indicates that the antitumor activities of chemotherapy also rely on several off-target effects, especially directed to the host immune system, that cooperate for successful tumor eradication. Chemotherapeutic agents stimulate both the innate and adaptive arms of the immune system through several modalities: (i) by promoting specific rearrangements on dying tumor cells, which render them visible to the immune system; (ii) by influencing the homeostasis of the hematopoietic compartment through transient lymphodepletion followed by rebound replenishment of immune cell pools; (iii) by subverting tumor-induced immunosuppressive mechanisms and (iv) by exerting direct or indirect stimulatory effects on immune effectors. Among the indirect ways of immune cell stimulation, some cytotoxic drugs have been shown to induce an immunogenic type of cell death in tumor cells, resulting in the emission of specific signals that trigger phagocytosis of cell debris and promote the maturation of dendritic cells, ultimately resulting in the induction of potent antitumor responses. Here, we provide an extensive overview of the multiple immune-based mechanisms exploited by the most commonly employed cytotoxic drugs, with the final aim of identifying prerequisites for optimal combination with immunotherapy strategies for the development of more effective treatments against cancer.

show abstract

Section: Effects On Tumor Cells and On Tumor Microenvironmentmentioning

confidence: 99%

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Depending on cells, conditions and stimuli, inhibition of caspase-8 can truly interrupt lethal signaling, favor a switch from apoptotic to necrotic cell death, [17][18][19] which depends on RIP1, 20,21 or induce (again RIP1-dependent) autophagic cell death. 22 Caspase inhibition has also been shown to lead to a switch from apoptosis to necrosis in, for example, thymocytes responding to DNA damage 23 or from apoptosis to autophagic cell death in, for example, growth factor-deprived neurons. 24 Furthermore, conditions that normally induce apoptosis through cellular stress (e.g.…”

Section: Inhibition/replacement Of Cell Death Typesmentioning

confidence: 99%

“…In animals, distinct mechanisms might intersect through shared molecules such as Beclin-1/Atg-6 (which interacts with the apoptosis regulator Bcl-2, yet is also essential for autophagy 22 ) or DAP kinase (a positive regulator of autophagy and apoptotic blebbing 43 ) or exert unidirectional inhibition of one on the other, as has been shown for proapoptotic caspases, which can repress necrosis 44 or antiapoptotic Bcl-XL which can facilitate autophagic cell death. 28 The latter interdeath mechanism inhibition, for which as yet there are only few examples, may well account for the masking of one mechanism by another in cells undergoing death.…”

Section: Inhibition/replacement Of Cell Death Typesmentioning

confidence: 99%

Redundant cell death mechanisms as relics and backups

Golstein

Kroemer

2005

Cell Death Differ

View full text Add to dashboard Cite

Here we review recent observations indicating the existence of redundant cell death mechanisms. We speculate that this redundancy reflects a particular evolutionary history for cellular demise. Autophagic or apoptotic elements might have been added to a primordial death mechanism, initially improving cell dismantling and later acquiring the ability to act themselves as death effectors. The resulting redundancy of cell death mechanisms has pathophysiological implications.

show abstract

“…Unlike apoptosis, which relies upon the activation of caspases that cleave hundreds of target proteins (24), autophagic cell death is usually thought of as caspase-independent (21). Indeed, two of the best examples of autophagic cell death where the demise of the cell was shown to require the autophagy machinery took place in cells with profound defects in the apoptosis machinery (25) or in the presence of caspase inhibitors (26). Cells undergoing autophagic cell death or apoptosis look different (27); the characteristic cellular morphology associated with apoptosis is usually due to caspase cleavage of cytoskeletal and other structural proteins (24) so that apoptotic cells show early degradation of the cytoskeleton but preserve organelles until fairly late in the process.…”

mentioning

confidence: 99%

Apoptosis and autophagy: regulatory connections between two supposedly different processes

2007

View full text Add to dashboard Cite

Apoptosis and autophagy are genetically-regulated, evolutionarily-conserved processes that regulate cell fate. Both apoptosis and autophagy are important in development and normal physiology and in a wide range of diseases. Recent studies show that despite the marked differences between these two processes, their regulation is intimately connected and the same regulators can sometimes control both apoptosis and autophagy. In this review, I discuss some of these findings, which provide possible molecular mechanisms for crosstalk between apoptosis and autophagy and suggest that it may be useful to think of these processes as different facets of the same cell death continuum rather than completely separate processes. KeywordsAutophagy; Apoptosis; Bcl-2, FADD; Atg 5In the early to mid 1990s there was a rapid increase in our understating about the regulation of apoptosis. Fifteen or so years later we are in the midst of a similarly exciting period for understanding autophagy with very rapid growth of publications on the regulation and function of this process (1). Autophagy (the form of autophagy discussed here is macroautophagy, other forms-microautophagy and chaperone-mediated autophagy share the same lysosomal degradation mechanism but differ in the way that material is delivered to the lysosome) is a degradative process involving sequestration of parts of the cytoplasm in double membrane vesicles (autophagic vesicles or autophagosomes) that fuse with lysosomes forming the autophagolysosome. In the autophagolysosome, the cytoplasmic material that was engulfed is hydrolyzed and the resulting amino acids and other macromolecular precursors can be recycled (2-4), see Fig 1 for a schematic of the process. Autophagy is a mechanism by which organelles are removed and is the primary degradation mechanism for long-lived proteins and thus maintains quality control for proteins and organelles. Autophagy is ubiquitous in eukaryotic cells and important in development and in diverse pathophysiological conditions (5)-for example providing protection against neurodegeneration (6,7), infections (8,9) and tumor development (10-13). Cells that are deficient in autophagy also demonstrate enhanced chromosomal instability (14,15), which may be related to the tumorigenesis associated with autophagy deficiency.Autophagy is important in cell death decisions and can protect cells by preventing them from undergoing apoptosis. For example, increased autophagy in nutrient deprived or growth factorwithdrawn cells allows cell survival (16,17) by inhibiting apoptosis. Autophagy also protects cells from various other apoptotic stimuli (18). It is not clear how autophagy stops cells from undergoing apoptosis; one suggested mechanism is the sequestration of damaged mitochondria (18) thus preventing released cytochrome c from being able to form a functional apoptosome NIH Public Access Autophagic cell death (also known as Type II programmed cell death to distinguish it from apoptosis or Type I programmed cell death) (20-22) has been describ...

show abstract

Regulation of an ATG7 - beclin 1 Program of Autophagic Cell Death by Caspase-8

Cited by 1,192 publications

References 25 publications

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

Redundant cell death mechanisms as relics and backups

Apoptosis and autophagy: regulatory connections between two supposedly different processes

Contact Info

Product

Resources

About