dapk1, encoding an activator of a p19ARF-p53-mediated apoptotic checkpoint, is a transcription target of p53

Martoriati, Alain; Doumont, Gilles; Alcalay, Myriam; Bellefroid, Éric; Pelicci, Pier Giuseppe; Marine, Jean–Christophe

doi:10.1038/sj.onc.1208256

Cited by 106 publications

(99 citation statements)

References 23 publications

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“…[42][43][44] DAPK has been shown to mediate cell death induced by a wide variety of stimuli, such as IFN-␥, TNF-␣, Fas, transforming growth factor-␤, DNA damage, c-Myc, E2F-1, endoplasmic reticulum stress, ceramide, matrix detachment, autophage, mitochondrial toxin, netrin-1 receptor UNC5H2, or cerebral ischemia. 20,21,25,29,37,[45][46][47][48] Our observations that DAPK promotes inflammasome assembly and caspase-1 activation reveal a potential role of DAPK in caspase-1-induced cell death. Caspase-1-mediated cell death is expected to be attenuated in DAPK-deficient cells because of diminished activation of caspase-1 (Figures 1-3), whereas increased caspase-1 activation in DAPK-overexpressing cell (Figure 4) shall result in enhanced cell death.…”

Section: Discussionmentioning

confidence: 90%

“…DAPK responds to calcium, a key factor in innate immune signaling, 50 and is connected to DNA damage through transcription activation by p53 or binding to p53. 45,46 Furthermore, DAPK is activated by ischemia 47 and constitutes a sensor for the mitochondrial membrane potential. 48 DAPK may also participate in the activation of NLRP3 inflammasome by bridging NLRP3 with DAPK-interacting proteins.…”

Section: Discussionmentioning

confidence: 99%

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Tumor suppressor death-associated protein kinase is required for full IL-1β production

Chuang

Lin

et al. 2011

Blood

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Interleukin-1␤ (IL-1␤ IntroductionInterleukin-1␤ (IL-1␤) plays an important role in infection and inflammation. 1 The generation of IL-1␤ is divided into 2 stages. In the first stage, inflammatory stimuli activate nuclear factor-B (NF-B) to promote the synthesis of pro-IL-1␤. In the second stage, pro-IL-1␤ protein is cleaved by caspase-1 to generate mature p17 IL-1␤ protein. The activation of caspase-1 is dependent on the formation of large multiprotein complexes inflammasomes in macrophages and monocytes. [2][3][4][5][6] Assembly of inflammasomes is stimulated by infection, inflammation, or danger signals. The NACHT domain-, leucine-rich repeat-, and pyrin domaincontaining protein 3 (NLRP3, also known as NALP3 or cryopyrin) inflammasome responds to a large array of stimulation, including microbial products, toxins, adenosine triphosphate (ATP), crystalline, aggregated particles. [7][8][9][10][11][12][13][14] The NLRP3 protein consists of an N-terminal pyrin domain for protein-protein interaction, a central NACHT domain for nucleotide binding and self-oligomerization, and C-terminal leucine-rich repeat motifs for ligand sensing. Mutation of the NLRP3 gene is associated with several autoinflammatory disorders, and NLRP3 is also linked to gout and diabetes. 5,15 Two signals are required for formation of NLRP3 inflammasome. NF-B-containing inflammatory signals activate NLRP3 expression. 16 A second inflammatory signal then stimulates the assembly of the NLRP3 inflammasome, through the binding of NLRP3 to apoptosis-associated speck-like protein containing a CARD domain (ASC) and recruitment of procaspase-1 molecule. Reactive oxygen species 10,13,17 and lysosomal protease cathepsin B 12,13 are potential activators of the NLRP3 inflammasome assembly. However, how inflammatory stimuli promote the formation of the NLRP3 inflammasome remains largely unclear. [2][3][4][5][6] In contrast, NLRP1 inflammasome has been successfully reconstituted in vitro with the recombinant proteins. 18 Part of the difficulties is the result of the spontaneous formation of inflammasome in vitro on cell membrane damage during the preparation of cell lysates. 19 Death-associated protein kinase (DAP-kinase, DAPk, or DAPK) is calcium/calmodulin-regulated Ser/Thr kinase that acts as a tumor suppressor. 20,21 Diminished DAPK expression is found in various types of cancer, including B lymphoma and chronic lymphocytic leukemia. 22-24 DAPK also mediates pathologic damages, such as N-methyl-D-aspartate receptor-triggered neuronal cell death. 25 DAPK is organized into multiple domains: an N-terminal kinase domain, followed by a calcium/calmodulin regulatory fragment, ankyrin repeats, a cytoskeleton binding region, and a C-terminal death domain. The multifunctional domains of DAPK are linked to diverse activities. 20,21 [26][27][28][29] and specific inhibition of T cell receptor-induced activation by DAPK. 30 DAPK is also part of a negative-feedback module in regulating the expression of inflammatory genes. 31 Recent studies reveal an intriguing interpl...

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Tumor suppressor death-associated protein kinase is required for full IL-1β production

Chuang

Lin

et al. 2011

Blood

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“…DAPK1 also inhibits microtubule-associated protein 1B (MAP1B; an LC3-interacting protein that inhibits autophagy). Similar to DRAM1, DAPK1 also has other functions beyond the regulation of autophagy and it is important to consider that additional functions might mediate the effects of DAPK1 with regards to tumour suppression (Martoriati et al, 2005) (Box 1).…”

Section: Regulation Of Autophagy By Oncogenes and Tumour Suppressorsmentioning

confidence: 99%

Autophagy and cancer – issues we need to digest

Liu

Ryan

2012

Journal of Cell Science

193

152

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SummaryAutophagy is an evolutionarily conserved catabolic pathway that has multiple roles in carcinogenesis and cancer therapy. It can inhibit the initiation of tumorigenesis through limiting cytoplasmic damage, genomic instability and inflammation, and the loss of certain autophagy genes can lead to cancer. Conversely, autophagy can also assist cells in dealing with stressful metabolic environments, thereby promoting cancer cell survival. In fact, some cancers rely on autophagy to survive and progress. Furthermore, tumour cells can exploit autophagy to cope with the cytotoxicity of certain anticancer drugs. By contrast, it appears that certain therapeutics require autophagy for the effective killing of cancer cells. Despite these dichotomies, it is clear that autophagy has an important, if complex, role in cancer. This is further exemplified by the fact that autophagy is connected with major cancer networks, including those driven by p53, mammalian target of rapamycin (mTOR), RAS and glutamine metabolism. In this Commentary, we highlight recent advances in our understanding of the role that autophagy has in cancer and discuss current strategies for targeting autophagy for therapeutic gain.This article is part of a Minifocus on Autophagy. For further reading, please see related articles: 'Ubiquitin-like proteins and autophagy at a glance' by Tomer Shpilka et al. (J. Cell Sci. 125, 2343-2348 and 'Autophagy and cell growth -the yin and yang of nutrient responses' by Thomas Neufeld (J. Cell Sci. 125, 2359-2368).

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“…15 The presence of p53-binding sites in the DAPk promotor sequence, and induction of DAPk expression by p53, indicate that a positive feedback loop may be operational in which DAPk and p53 activate each other. 66 An additional connection between the DAPk family and the p53 pathway came from a phage-peptide display analysis, which led to the identification of ZIPk as an Mdm2 and p21-interacting protein. 64 ZIPk phosphorylated peptides from both interacting proteins, indicating the presence of another level of regulation of the p53 pathway by the DAPk family.…”

Section: Dapk Family and Cancer: A Novel Tumor Suppressor Family Of Pmentioning

confidence: 99%

DAPk Protein Family and Cancer

Gözüaçık¹,

Kimchi²

2006

Autophagy

189

172

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The Death-Associated Protein kinase (DAPk) family contains three closely related serine/threonine kinases, named DAPk, ZIPk and DRP-1, which display a high degree of homology in their catalytic domains. The recent discovery of protein-protein interactions and kinase/substrate relationships among these family members suggests that the three kinases may form multi-protein complexes capable of transmitting apoptotic or autophagic cell death signals in response to various cellular stresses including the misregulated expression of oncogenes in premalignant cells. Several lines of evidence indicate that the most studied member of the family, DAPk, has tumor and metastasis suppressor properties. Here we present an overview of the data connecting the DAPk family of proteins to cell death and malignant transformation and discuss the possible involvement of the autophagic cell death-inducing capacity of DAPk in its tumor suppressor activity.

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dapk1, encoding an activator of a p19ARF-p53-mediated apoptotic checkpoint, is a transcription target of p53

Cited by 106 publications

References 23 publications

Tumor suppressor death-associated protein kinase is required for full IL-1β production

Tumor suppressor death-associated protein kinase is required for full IL-1β production

Autophagy and cancer – issues we need to digest

DAPk Protein Family and Cancer

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