Distinct functions of the dual leucine zipper kinase depending on its subcellular localization

Wallbach, Manuel; Escobar, Jorge Duque; Babaeikelishomi, Rohollah; Stahnke, Marie-Jeannette; Blume, Roland; Schröder, Sabine; Kruegel, Jenny; Maedler, Kathrin; Kluth, Oliver; Kehlenbach, Ralph H.; Miosge, Nicolai; Oetjen, Elke

doi:10.1016/j.cellsig.2016.01.002

Cited by 19 publications

(25 citation statements)

References 82 publications

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“…4 ). Additionally, the protein’s function is related to its localization in some way 42 . Based on the subcellular localization predictions, most ClNACs probably function in the nucleus, while others were located in different organelles or the cytoplasm.…”

Section: Resultsmentioning

confidence: 99%

Global Expressions Landscape of NAC Transcription Factor Family and Their Responses to Abiotic Stresses in Citrullus lanatus

Lan

Guy

et al. 2016

Sci Rep

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Watermelon (Citrullus lanatus) is one xerophyte that has relative higher tolerance to drought and salt stresses as well as more sensitivity to cold stress, compared with most model plants. These characteristics facilitate it a potential model crop for researches on salt, drought or cold tolerance. In this study, a genome-wide comprehensive analysis of the ClNAC transcription factor (TF) family was carried out for the first time, to investigate their transcriptional profiles and potential functions in response to these abiotic stresses. The expression profiling analysis reveals that several NAC TFs are highly responsive to abiotic stresses and development, for instance, subfamily IV NACs may play roles in maintaining water status under drought or salt conditions, as well as water and metabolites conduction and translocation toward fruit. In contrast, rapid and negative responses of most of the ClNACs to low-temperature adversity may be related to the sensitivity to cold stress. Crosstalks among these abiotic stresses and hormone (abscisic acid and jasmonic acid) pathways were also discussed based on the expression of ClNAC genes. Our results will provide useful insights for the functional mining of NAC family in watermelon, as well as into the mechanisms underlying abiotic tolerance in other cash crops.

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Section: Resultsmentioning

confidence: 99%

Global Expressions Landscape of NAC Transcription Factor Family and Their Responses to Abiotic Stresses in Citrullus lanatus

Lan

Guy

et al. 2016

Sci Rep

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“…Thus, apart from the well-accepted roles for JNKs in their phosphorylation of nuclear substrates, their roles in regulating cytoplasmic targets and mitochondrial proteins are emerging. In addition, studies on upstream kinases have begun to reveal the importance of their localization in influencing JNK pathway actions (466,467). More indepth analyses of compartmentalization of JNK signaling will require greater development and use of biosensors capable of reporting JNK activities in different subcellular locations.…”

Section: Discussionmentioning

confidence: 99%

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

Zeke

Misheva

Reményi

et al. 2016

Microbiol Mol Biol Rev

386

350

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SUMMARYThe c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states.

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“…The pro‐inflammatory cytokines TNFα and IL 1β induce the translocation of DLK to the nucleus. The nuclear localization of DLK is required for induction of beta‐cell apoptosis and prolonging the nuclear localization of DLK by mutating its nuclear export signal exacerbates TNFα‐induced apoptosis . In a mouse model of prediabetes, increased nuclear localization of DLK was found.…”

Section: Reduction Of Beta‐cell Mass By the Dual Leucine Zipper Kinasementioning

confidence: 99%

“…In a mouse model of prediabetes, increased nuclear localization of DLK was found. Furthermore, only nuclear DLK inhibited the activity of the transcription factor cAMP response element binding protein (CREB) and DLK induced inhibitory phosphorylation of a CREB coactivator and prevented its promoter recruitment . CREB is ubiquitously expressed and mediates such diverse processes as learning and memory and glucose homeostasis .…”

Section: Reduction Of Beta‐cell Mass By the Dual Leucine Zipper Kinasementioning

confidence: 99%

“…Furthermore, glucose and glucagon‐like peptide‐1 (GLP‐1) stimulate CREB transcriptional activity at various levels . Hence, the inhibition of CREB‐dependent gene transcription, important for beta‐cell survival and function, by nuclear DLK, elicited by the prediabetic signals TNFα and IL 1β, contributes to the pathogenesis of diabetes mellitus type 2 .…”

Section: Reduction Of Beta‐cell Mass By the Dual Leucine Zipper Kinasementioning

confidence: 99%

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Regulation of Beta‐Cell Function and Mass by the Dual Leucine Zipper Kinase

Oetjen

2016

Archiv der Pharmazie

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Diabetes mellitus is one of the most rapidly increasing diseases worldwide, whereby approximately 90-95% of patients suffer from type 2 diabetes. Considering its micro- and macrovascular complications like blindness and myocardial infarction, a reliable anti-diabetic treatment is needed. Maintaining the function and the mass of the insulin producing beta-cells despite elevated levels of beta-cell-toxic prediabetic signals represents a desirable mechanism of action of anti-diabetic drugs. The dual leucine zipper kinase (DLK) inhibits the action of two transcription factors within the beta-cell, thereby interfering with insulin secretion and production and the conservation of beta-cell mass. Furthermore, DLK action is regulated by prediabetic signals. Hence, the inhibition of this kinase might protect beta-cells against beta-cell-toxic prediabetic signals and prevent the development of diabetes. DLK might thus present a novel drug target for the treatment of diabetes mellitus type 2.

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Distinct functions of the dual leucine zipper kinase depending on its subcellular localization

Cited by 19 publications

References 82 publications

Global Expressions Landscape of NAC Transcription Factor Family and Their Responses to Abiotic Stresses in Citrullus lanatus

Global Expressions Landscape of NAC Transcription Factor Family and Their Responses to Abiotic Stresses in Citrullus lanatus

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

Regulation of Beta‐Cell Function and Mass by the Dual Leucine Zipper Kinase

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