DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress

Eisenberg‐Lerner, Avital; Kimchi, Adi

doi:10.1038/sj.cdd.4402212

Cited by 94 publications

(75 citation statements)

References 24 publications

(41 reference statements)

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“…34 Furthermore, DAPK regulates JNK signaling by binding and activating protein kinase D under conditions of oxidative stress. 35 Future studies are required to define the crosstalk between the MAP kinases (e.g., JNK, ERK) and DAPK to regulate phosphorylation/ dephosphorylation events in autophagy. (3) Competitive displacement of Bcl-2 by other Beclin 1-binding proteins such as HMGB1, UVRAG or Atg14L/Barkor; this likely initiates a program of heightened anti-apoptotic state, promotes autophagy, and ultimately protects the cell during cell stress.…”

Section: Inhibition Of Autophagy By Beclin 1-bcl-2 /Bcl-xl Complexesmentioning

confidence: 99%

The Beclin 1 network regulates autophagy and apoptosis

et al. 2011

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Beclin 1, the mammalian orthologue of yeast Atg6, has a central role in autophagy, a process of programmed cell survival, which is increased during periods of cell stress and extinguished during the cell cycle. It interacts with several cofactors (Atg14L, UVRAG, Bif-1, Rubicon, Ambra1, HMGB1, nPIST, VMP1, SLAM, IP 3 R, PINK and survivin) to regulate the lipid kinase Vps-34 protein and promote formation of Beclin 1-Vps34-Vps15 core complexes, thereby inducing autophagy. In contrast, the BH3 domain of Beclin 1 is bound to, and inhibited by Bcl-2 or Bcl-XL. This interaction can be disrupted by phosphorylation of Bcl-2 and Beclin 1, or ubiquitination of Beclin 1. Interestingly, caspase-mediated cleavage of Beclin 1 promotes crosstalk between apoptosis and autophagy. Beclin 1 dysfunction has been implicated in many disorders, including cancer and neurodegeneration. Here, we summarize new findings regarding the organization and function of the Beclin 1 network in cellular homeostasis, focusing on the cross-regulation between apoptosis and autophagy. Cell Death and Differentiation (2011) 18, 571-580; doi:10.1038/cdd.2010 published online 11 February 2011 Autophagy is an essential process that consists of selective degradation of cellular components. There are at least three different types of autophagy described and possibly more. These autophagy types include macroautophagy (hereafter referred to as autophagy), microautophagy and chaperonemediated autophagy. 1 The initial step of autophagy is the surrounding and sequestering of cytoplasmic organelles and proteins within an isolation membrane (phagophore). Potential sources for the membrane to generate the phagophore include the Golgi complex, endosomes, the endoplasmic reticulum (ER), mitochondria and the plasma membrane. 2 The nascent membranes are fused at their edges to form double-membrane vesicles, called autophagosomes. Autophagosomes undergo a stepwise maturation process, including fusion with acidified endosomal and/or lysosomal vesicles, eventually leading to the delivery of cytoplasmic contents to lysosomal components, where they fuse, then degrade and are recycled (Figure 1a). The process of mammalian autophagy is divided into six principal steps: initiation (Figure 1b It has been well demonstrated that autophagy depends on Atg5/Atg7, is associated with microtubule-associated protein light chain 3 (LC3) truncation and lipidation, and may originate directly from the ER membrane and other membrane organelles. Furthermore, recent study has identified a Atg5/Atg7-independent pathway of autophagy. 3 This pathway of autophagy was not associated with LC3 processing but appeared to involve autophagosome formation from late endosomes and the trans-Golgi. 3 Atg7-independent autophagy had been implicated in mitochondrial clearance from reticulocytes. 4 The exact molecular basis of Atg5/Atg7-independent autophagy remains to be elucidated. Interestingly, Beclin 1 is required for Atg5/Atg7-dependent and -independent autophagy. 3 However, the presence of Beclin 1-indep...

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Section: Inhibition Of Autophagy By Beclin 1-bcl-2 /Bcl-xl Complexesmentioning

confidence: 99%

The Beclin 1 network regulates autophagy and apoptosis

et al. 2011

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“…79 DAPk has also recently been shown to phosphorylate PKD, which leads to the activation of JNK and necrotic cell death during oxidative stress. 80 E2F1. The E2F family of transcription factors has been implicated in various signaling pathways leading to cell death and survival.…”

Section: Cross-talk Between Autophagy and Apoptosismentioning

confidence: 99%

Life and death partners: apoptosis, autophagy and the cross-talk between them

et al. 2009

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It is not surprising that the demise of a cell is a complex well-controlled process. Apoptosis, the first genetically programmed death process identified, has been extensively studied and its contribution to the pathogenesis of disease well documented. Yet, apoptosis does not function alone to determine a cell's fate. More recently, autophagy, a process in which de novo-formed membrane-enclosed vesicles engulf and consume cellular components, has been shown to engage in a complex interplay with apoptosis. In some cellular settings, it can serve as a cell survival pathway, suppressing apoptosis, and in others, it can lead to death itself, either in collaboration with apoptosis or as a back-up mechanism when the former is defective. The molecular regulators of both pathways are inter-connected; numerous death stimuli are capable of activating either pathway, and both pathways share several genes that are critical for their respective execution. The cross-talk between apoptosis and autophagy is therefore quite complex, and sometimes contradictory, but surely critical to the overall fate of the cell. Furthermore, the crosstalk is a key factor in the outcome of death-related pathologies such as cancer, its development and treatment. Autophagy, a process long known to provide a survival advantage to cells undergoing nutrient deprivation or other stresses, has also been more recently linked to the actual death process itself. Thus apoptosis is not the sole means by which the cell can undergo a genetically programmed regulated process by which it undergoes self-elimination. Cell death can occur by several mechanisms and the phenotypic changes that accompany cell death can vary depending on the stimulus and cell setting. In any given death scenario, the cell decides which pathway to use, depending on the nature of the stimulus and the particulars of the cell environment. Furthermore, apoptosis and autophagy are not mutually exclusive pathways. They have been shown to act in synergy and also to counter each other. They share many of the same molecular regulators. In a clinical setting, one cannot predict the outcome of inhibition or activation of one death program without considering the effect on the other. This review will focus on the cross-talk between the autophagic and apoptotic pathways, with an analysis of how this may affect the clinical applications of death suppression/activation to cancer. The process of necrosis, the third means by which the cell can undergo a genetically programmed self-elimination, will not be discussed in detail. Although not intended to provide an exhaustive summary of the recent literature, the discussion will include salient experimental results as examples of the different facets of the apoptosis/autophagy interplay.An issue that has been raised and discussed in the literature is that in many cell settings, autophagy accompanies, rather than causes, cell death. 1 This argument is based on the fact that many studies that claim autophagic cell death prove that autophagy occurs, and that ...

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“…14 Finally, necroptosis is characterized by the relatively smallest number of regulators. Typically, necroptosis is modulated by c-Jun N-terminal kinase (JNK), apoptosis inducing factor (AIF), death-associated protein kinase (DAPK), and reactive oxygen species, [15][16][17][18] whereas in the apoptosis-incompetent cells, necroptosis is activated by death receptors and involves the RIP1 kinase. 19 Among the various roles of PCD in maintaining the homeostasis of living organisms is its involvement in the advancement of immune responses.…”

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confidence: 99%

Resilience of death: intrinsic disorder in proteins involved in the programmed cell death

et al. 2013

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It is recognized now that intrinsically disordered proteins (IDPs), which do not have unique 3D structures as a whole or in noticeable parts, constitute a significant fraction of any given proteome. IDPs are characterized by an astonishing structural and functional diversity that defines their ability to be universal regulators of various cellular pathways. Programmed cell death (PCD) is one of the most intricate cellular processes where the cell uses specialized cellular machinery and intracellular programs to kill itself. This cell-suicide mechanism enables metazoans to control cell numbers and to eliminate cells that threaten the animal's survival. PCD includes several specific modules, such as apoptosis, autophagy, and programmed necrosis (necroptosis). These modules are not only tightly regulated but also intimately interconnected and are jointly controlled via a complex set of protein-protein interactions. To understand the role of the intrinsic disorder in controlling and regulating the PCD, several large sets of PCD-related proteins across 28 species were analyzed using a wide array of modern bioinformatics tools. This study indicates that the intrinsic disorder phenomenon has to be taken into consideration to generate a complete picture of the interconnected processes, pathways, and modules that determine the essence of the PCD. We demonstrate that proteins involved in regulation and execution of PCD possess substantial amount of intrinsic disorder. We annotate functional roles of disorder across and within apoptosis, autophagy, and necroptosis processes. Disordered regions are shown to be implemented in a number of crucial functions, such as protein-protein interactions, interactions with other partners including nucleic acids and other ligands, are enriched in post-translational modification sites, and are characterized by specific evolutionary patterns. We mapped the disorder into an integrated network of PCD pathways and into the interactomes of selected proteins that are involved in the p53-mediated apoptotic signaling pathway.

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DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress

Cited by 94 publications

References 24 publications

The Beclin 1 network regulates autophagy and apoptosis

The Beclin 1 network regulates autophagy and apoptosis

Life and death partners: apoptosis, autophagy and the cross-talk between them

Resilience of death: intrinsic disorder in proteins involved in the programmed cell death

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