DAPK-ZIPK-L13a Axis Constitutes a Negative-Feedback Module Regulating Inflammatory Gene Expression

Mukhopadhyay, Rupak; Ray, Partho Sarothi; Arif, Abul; Brady, Anna K.; Kinter, Michael; Fox, Paul L.

doi:10.1016/j.molcel.2008.09.019

Cited by 133 publications

(159 citation statements)

References 52 publications

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“…However, in a biological context the RNAbinding activity of RBPs is typically regulated by a plethora of mechanisms, including post-translational modifications (Mukhopadhyay et al 2008;Arif et al 2009), induced conformational changes (Walden et al 2006;Siddiqui et al 2012), competition with other RBPs for target RNAs (Yao et al 2012), differential subcellular localization (Alvarez et al 2013), alterations of its expression levels, or the availability of its target RNAs. Importantly, most of the proteins within the HeLa mRNA interactome are post-translationally modified (http://www.embl.de/mRNAinteractome) (Castello et al 2012), suggesting that RBPs may globally respond to environmental alterations.…”

Section: Discussionmentioning

confidence: 99%

A versatile assay for RNA-binding proteins in living cells

Strein

Alleaume

Rothbauer

et al. 2014

RNA

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RNA-binding proteins (RBPs) control RNA fate from synthesis to decay. Since their cellular expression levels frequently do not reflect their in vivo activity, methods are needed to assess the steady state RNA-binding activity of RBPs as well as their responses to stimuli. While electrophoresis mobility shift assays (EMSA) have been used for such determinations, their results serve at best as proxies for the RBP activities in living cells. Here, we describe a quantitative dual fluorescence method to analyze protein-mRNA interactions in vivo. Known or candidate RBPs are fused to fluorescent proteins (eGFP, YFP), expressed in cells, cross-linked in vivo to RNA by ultraviolet light irradiation, and immunoprecipitated, after lysis, with a single chain antibody fragment directed against eGFP (GFP-binding protein, GBP). Polyadenylated RNA-binding activity of fusion proteins is assessed by hybridization with an oligo(DT) probe coupled with a red fluorophore. Since UV light is directly applied to living cells, the assay can be used to monitor dynamic changes in RNA-binding activities in response to biological or pharmacological stimuli. Notably, immunoprecipitation and hybridization can also be performed with commercially available GBP-coupled 96-well plates (GFP-multiTrap), allowing highly parallel RNA-binding measurements in a single experiment. Therefore, this method creates the possibility to conduct in vivo high-throughput RNA-binding assays. We believe that this fast and simple radioactivity-free method will find many useful applications in RNA biology.

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Section: Discussionmentioning

confidence: 99%

A versatile assay for RNA-binding proteins in living cells

Strein

Alleaume

Rothbauer

et al. 2014

RNA

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“…10 It was further reported that DAPK3 regulates inflammatory signalings, including ribosomal protein L13a, extracellular signal-regulated kinase, and interferon-γ-activated inhibitor of translation in macrophages. 12 Vascular inflammation is known to be an important process for the development of hypertension at an early stage. In addition, a critical role for inflammation induced by ROS has been suggested in hypertension.…”

Section: Hypertensionmentioning

confidence: 99%

Death-Associated Protein Kinase 3 Mediates Vascular Inflammation and Development of Hypertension in Spontaneously Hypertensive Rats

et al. 2012

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C almodulin (CaM) is recognized as a key regulatory molecule for diverse biological functions, such as muscular contraction.1 In addition, a recent study demonstrated that CaM-dependent protein kinases, such as CaM-dependent protein kinase II, may regulate hypertension through the mechanisms including promotion of vascular smooth muscle hypertrophy. 2 In the previous study, we compared expression levels of several CaM-related proteins with almost unknown functions in vasculature. As a result, we demonstrated that protein expression of eukaryotic elongation factor 2 kinase (also known as CaM-dependent protein kinase III), histone deacetylase 4, and death associated protein kinase (DAPK) 3 increased in the mesenteric artery from spontaneously hypertensive rats (SHRs) compared with Wistar Kyoto rats (WKYs). 3 In the recent study, we also showed that histone deacetylase 4 promotes reactive oxygen species (ROS)-dependent vascular inflammation and mediates the development of hypertension in SHRs. 4 However, it remains to be clarified how DAPK3, might affect vascular patholophysiology and control the development of hypertension. The DAPK protein has been considered as a Ca 2+ /CaMregulated serine/threonine kinase that mainly mediates cell death. 5 The DAPK protein consists of multiple domains, including an N-terminal kinase domain (known as a Ca 2+ /CaM regulatory region), ankyrin repeats, a cytoskeleton binding region, and a C-terminal death domain.6 Various stimulation-induced intracellular calcium spikes promote the CaM binding to the CaM regulatory region of DAPK, which in turn activates DAPK.7 Five protein kinases, including DAPK1, DAPK2, DAPK3 (also known as Zipper-interacting protein kinase), DAPK-related apoptosis-inducing protein kinase 1, and DAPK-related apoptosis-inducing protein kinase 2, are known as DAPK family proteins.8 DAPK1, DAPK2, and DAPK3 are all ubiquitously expressed in various tissues from mice and rats.6 Recently, the functions of DAPK3 were gradually clarified. The mutation of DAPK3 Abstract-Death-associated protein kinase (DAPK) is a Ca 2+ /calmodulin-regulated serine/threonine kinase that mediates cell death. Our recent study demonstrated that DAPK3 protein increases in the mesenteric artery from spontaneously hypertensive rats compared with Wistar Kyoto rats. Pathogenesis of hypertension is modulated at least in part by vascular inflammation. We examined whether DAPK3 mediates vascular inflammatory responses and development of hypertension. In rat mesenteric arterial smooth muscle cells, small interfering RNA against DAPK3 inhibited vascular cell adhesion molecule 1 expression and monocyte adhesion induced by tumor necrosis factor-α. DAPK3 small interfering RNA inhibited phosphorylation of c-Jun amino-terminal kinase, p38, and Akt, as well as reactive oxygen species (ROS) production induced by tumor necrosis factor-α. In human umbilical vein endothelial cells, expressions of vascular cell adhesion molecule 1, endothelial selectin, and cyclooxygenase 2, as well as ROS production induced ...

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“…30 DAPK is also part of a negative-feedback module in regulating the expression of inflammatory genes. 31 Recent studies reveal an intriguing interplay between inflammasomes and autophagy. Caspase-1 activation suppresses Shigellainduced autophagy, 32 whereas autophagy inhibits activation of inflammasome.…”

Section: Introductionmentioning

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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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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DAPK-ZIPK-L13a Axis Constitutes a Negative-Feedback Module Regulating Inflammatory Gene Expression

Cited by 133 publications

References 52 publications

A versatile assay for RNA-binding proteins in living cells

A versatile assay for RNA-binding proteins in living cells

Death-Associated Protein Kinase 3 Mediates Vascular Inflammation and Development of Hypertension in Spontaneously Hypertensive Rats

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

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