Inhibited Neurogenesis in JNK1-Deficient Embryonic Stem Cells

Amura, Claudia R.; Marek, Lindsay A.; Winn, Robert A.; Heasley, Lynn E.

doi:10.1128/mcb.25.24.10791-10802.2005

Cited by 60 publications

(46 citation statements)

References 43 publications

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“…Furthermore, different JNK gene knockout mice showed that JNK1 and JNK2 regulate fibroblasts, macrophages, and T cells differently (163,183,184) and also influence skin wound repair differently (185). Neurogenesis in vitro also primarily requires JNK1, but not JNK2 or JNK3 (186). Maintenance of metabolic homeostasis required both JNK1 and JNK2, but JNK1 played more important roles (187).…”

Section: Comparison Of Jnk1 and Jnk2 Functions In Vivomentioning

confidence: 99%

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

Zeke

Misheva

Reményi

et al. 2016

Microbiol Mol Biol Rev

409

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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Section: Comparison Of Jnk1 and Jnk2 Functions In Vivomentioning

confidence: 99%

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

Zeke

Misheva

Reményi

et al. 2016

Microbiol Mol Biol Rev

409

350

View full text Add to dashboard Cite

show abstract

“…Further experiments will be required to support the proposed pathway leading to effects on dendritic architecture through microtubule-associated protein 2 phosphorylation by JNK. However, JNK1 has now been implicated in the dendritic architecture of the cerebellum and motor cortex (28), in addition to maintaining normal brain axonal growth (51) and contributing to the repression of Wnt (Wnt-4 and Wnt-6) expression and neural differentiation (as recently modeled in embryonic stem cells) (10). It is therefore possible that a complex range of JNK1 substrates regulates these biological processes in vivo.…”

Section: Jnk Interaction With and Phosphorylation Of Microtubuleassocmentioning

confidence: 99%

Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases

Bogoyevitch

Kobe

2006

Microbiol Mol Biol Rev

530

477

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SUMMARY The c-Jun N-terminal kinases (JNKs) are members of a larger group of serine/threonine (Ser/Thr) protein kinases from the mitogen-activated protein kinase family. JNKs were originally identified as stress-activated protein kinases in the livers of cycloheximide-challenged rats. Their subsequent purification, cloning, and naming as JNKs have emphasized their ability to phosphorylate and activate the transcription factor c-Jun. Studies of c-Jun and related transcription factor substrates have provided clues about both the preferred substrate phosphorylation sequences and additional docking domains recognized by JNK. There are now more than 50 proteins shown to be substrates for JNK. These include a range of nuclear substrates, including transcription factors and nuclear hormone receptors, heterogeneous nuclear ribonucleoprotein K, and the Pol I-specific transcription factor TIF-IA, which regulates ribosome synthesis. Many nonnuclear substrates have also been characterized, and these are involved in protein degradation (e.g., the E3 ligase Itch), signal transduction (e.g., adaptor and scaffold proteins and protein kinases), apoptotic cell death (e.g., mitochondrial Bcl2 family members), and cell movement (e.g., paxillin, DCX, microtubule-associated proteins, the stathmin family member SCG10, and the intermediate filament protein keratin 8). The range of JNK actions in the cell is therefore likely to be complex. Further characterization of the substrates of JNK should provide clearer explanations of the intracellular actions of the JNKs and may allow new avenues for targeting the JNK pathways with therapeutic agents downstream of JNK itself.

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“…Indeed, growing literature supports a role of JNK in cell proliferation, survival, and differentiation. For instance, it was shown that JNK1 and the JNK pathway-specific scaffold protein, JSAP1, promote neural differentiation of embryonic stem cells [45,46]. Activated JNK may also foster axonogenesis and neuronal polarization by targeting cytoskeletal proteins, such as the Tau protein [47,48].…”

Section: Mir-124 Nps Promote Axonogenesismentioning

confidence: 99%

MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson's disease

Saraiva

Paiva

Santos

et al. 2016

Journal of Controlled Release

144

128

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Modulation of the subventricular zone (SVZ) neurogenic niche can enhance brain repair in several disorders including Parkinson's disease (PD). Herein, we used biocompatible and traceable polymeric nanoparticles (NPs) containing perfluoro-1,5-crown ether (PFCE) and coated with protamine sulfate to complex microRNA-124 (miR-124), a neuronal fate determinant. The ability of NPs to efficiently deliver miR-124 and prompt SVZ neurogenesis and brain repair in PD was evaluated. In vitro, miR-124 NPs were efficiently internalized by neural stem/progenitors cells and neuroblasts and promoted their neuronal commitment and maturation. The expression of Sox9 and Jagged1, two miR-124 targets and stemness-related genes, were also decreased upon miR-124 NP treatment. In vivo, the intracerebral administration of miR-124 NPs increased the number of migrating neuroblasts that reached the granule cell layer of the olfactory bulb, both in healthy and in a 6-hydroxydopamine (6-OHDA) mouse model for PD.MiR-124 NPs were also able to induce migration of neurons into the lesioned striatum of 6-OHDA-treated mice. Most importantly, miR-124 NPs proved to ameliorate motor symptoms of 6-OHDA mice, monitored by the apomorphine-induced rotation test.Altogether, we provide clear evidences to support the use of miR-124 NPs as a new therapeutic approach to boost endogenous brain repair mechanisms in a setting of neurodegeneration.

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Inhibited Neurogenesis in JNK1-Deficient Embryonic Stem Cells

Abstract: The JNKs are components of stress signaling pathways but also regulate morphogenesis and differentiation. Previously, we invoked a role for the JNKs in nerve growth factor (

Cited by 60 publications

References 43 publications

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

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

Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases

MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson's disease

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