Essential Roles of Atg5 and FADD in Autophagic Cell Death

Pyo, Jong Ok; Jang, Mi; Kwon, Young–Kyu; Lee, Ho June; Jun, Joon Il; Woo, Ha-Na; Cho, Dong Hyung; Choi, Bo Youn; Lee, Heuiran; Kim, Joo Hang; Mizushima, Noboru; Oshumi, Yoshinori; Jung, Yong‐Keun

doi:10.1074/jbc.m413934200

Cited by 472 publications

(178 citation statements)

References 29 publications

(32 reference statements)

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“…On the other hand, the study by Pyo et al 26 suggests that an autophagy protein (Atg5) can interact with an apoptosis protein (FADD). This Bcl-x L is not known to be required for starvation-induced autophagy.…”

Section: Discussionmentioning

confidence: 99%

“…The articles discussed above 16,17 show for the first time in mammalian cells that autophagy proteins are needed for survival under nutrient starvation. On the other hand, the three cell death studies 21,24,26 show for the first time that autophagic cell death is dependent on autophagy proteins (Atg5, Atg7, and beclin 1) that are needed for the formation of new autophagosomes. This demonstrates that the formation of autophagosomes is needed for the cell death, and that under certain conditions autophagy can initiate and/or execute cell death.…”

Section: Discussionmentioning

confidence: 99%

“…Pyo et al 26 recently published a further study demonstrating that autophagic cell death is dependent on an autophagy protein, using cells that undergo autophagic cell death after interferon-g treatment. First the authors showed that downregulation of Atg5 expression suppressed both autophagic vacuole formation and cell death in HeLa cells treated with interferon-g. Inversely, overexpression of Atg5 induced autophagic cell death.…”

Section: Autophagy Genes Are Needed For Autophagic Cell Deathmentioning

confidence: 99%

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Doctor Jekyll and Mister Hyde: autophagy can promote both cell survival and cell death

Eskelinen

2005

Cell Death Differ

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Via autophagy cells can degrade their own cytoplasmic material in lysosomes. This process has been considered important for survival during starvation conditions, but the genetic evidence for such a role in mammalian cells has been lacking. Recent results with cell lines deficient in autophagy proteins finally demonstrate the essential role of autophagy for survival in mammalian cells deprived of nutrients or growth factors. However, recent results also show that under certain conditions autophagy can promote cell death, particularly if cells are triggered to die but apoptosis is not possible. Importantly, these studies show that autophagy proteins are needed for the induction or execution of cell death. However, the current results suggest that the two modes of autophagy, survival promoting and death promoting, may be activated via different signaling pathways. In addition, further results suggest that under certain conditions autophagy may act as an initiator of cell death that however needs the apoptotic machinery for the execution of the cell demise.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Autophagy Genes Are Needed For Autophagic Cell Deathmentioning

confidence: 99%

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Doctor Jekyll and Mister Hyde: autophagy can promote both cell survival and cell death

Eskelinen

2005

Cell Death Differ

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“…However, we could not identify specific sequences predicted to form CARD or CARD-like domains in Atg5. In addition, previous reports have shown the possibility of Atg5 interaction with Fasassociated protein with death domain or Bcl-X L (28,32). Further analysis using site-directed mutagenesis or crystal structure is needed to identify precise domains and the amino acids of Atg5 required for such interactions.…”

Section: Discussionmentioning

confidence: 99%

The Atg5–Atg12 conjugate associates with innate antiviral immune responses

Jounai

Takeshita

Kobiyama

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

513

499

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Autophagy is an essential process for physiological homeostasis, but its role in viral infection is only beginning to be elucidated. We show here that the Atg5-Atg12 conjugate, a key regulator of the autophagic process, plays an important role in innate antiviral immune responses. Atg5-deficient mouse embryonic fibroblasts (MEFs) were resistant to vesicular stomatitis virus replication, which was largely due to hyperproduction of type I interferons in response to immunostimulatory RNA (isRNA), such as virus-derived, double-stranded, or 5 -phosphorylated RNA. Similar hyperresponse to isRNA was also observed in Atg7-deficient MEFs, in which Atg5-Atg12 conjugation is impaired. Overexpression of Atg5 or Atg12 resulted in Atg5-Atg12 conjugate formation and suppression of isRNA-mediated signaling. Molecular interaction studies indicated that the Atg5-Atg12 conjugate negatively regulates the type I IFN production pathway by direct association with the retinoic acid-inducible gene I (RIG-I) and IFN-␤ promoter stimulator 1 (IPS-1) through the caspase recruitment domains (CARDs). Thus, in contrast to its role in promoting the bactericidal process, a component of the autophagic machinery appears to block innate antiviral immune responses, thereby contributing to RNA virus replication in host cells.innate immunity ͉ signal transduction ͉ type I interferon

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“…3 Furthermore, several studies have reported interactions between the ATG5-12 complexes and the extrinsic apoptotic adapter protein FADD; these interactions recruit FADD to autophagosomes. [4][5][6] In this issue, Basit et al 1 provide convincing evidence for autophagy-driven cell death mediated by these interactions. They show that the treatment of rhabdomyosarcoma cells with the pan-Bcl-2 family inhibitor Obatoclax (also called GX15-070) leads to massive autophagy and potent cell death; surprisingly however, they demonstrate that this cell death is not caspasedependent apoptosis, but rather receptor interacting protein kinase-1 (RIPK1) and RIPK3-dependent necroptosis.…”

mentioning

confidence: 99%

Autophagic cell death RIPs into tumors

Oberst

2013

Cell Death Differ

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Essential Roles of Atg5 and FADD in Autophagic Cell Death

Cited by 472 publications

References 29 publications

Doctor Jekyll and Mister Hyde: autophagy can promote both cell survival and cell death

Doctor Jekyll and Mister Hyde: autophagy can promote both cell survival and cell death

The Atg5–Atg12 conjugate associates with innate antiviral immune responses

Autophagic cell death RIPs into tumors

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