A ternary complex consisting of AICD, FE65, and TIP60 down-regulates Stathmin1

Müller, Thorsten; Schrötter, Andreas; Looße, Christina; Pfeiffer, Kathy; Theiß, Carsten; Kauth, Marion; Meyer, Helmut E.; Marcus, Katrin

doi:10.1016/j.bbapap.2012.07.017

Cited by 36 publications

(20 citation statements)

References 47 publications

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“…Potential target genes of AICD nuclear signaling include retinoic acid-responsive genes (Gao and Pimplikar, 2001), KAI1/CD82 (Baek et al, 2002), glycogen synthase kinase-3β (GSK3β) (Kim et al, 2003), APP, BACE1, Tip60 (Von Rotz et al, 2004), NEP (Pardossi-Piquard et al, 2005), p53 (Alves da Costa et al, 2006), Fibronectin1 (FN1), α2-actin, transgelin (SM22), tropomyosin 1 (TPM1), flavoprotein oxidoreductase MICAL2 (MICAL2), Ras-associated protein (RAB3B) (Muller et al, 2007), EGF receptor (EGFR) (Zhang et al, 2007), LRP (LRP1) (Liu et al, 2007), Cyclins B1 and D1 (Ahn et al, 2008), vesicular glutamate transporter (VGLUT2) (Schrenk-Siemens et al, 2008), C/EBP homologous protein (CHOP) (Takahashi et al, 2009), Aquaporin 1 (Huysseune et al, 2009), S100a9 (Ha et al, 2010), ApoJ/clusterin (Kogel et al, 2012), patched homolog 1 (Ptch1), transient receptor potential cation channel subfamily C member 5 (TRPC5) (Das et al, 2011), serine-palmitoyl transferase (SPT) subunit SPTLC2 (Grimm et al, 2011a), alkyl-dihydroxyacetonephosphate-synthase (AGPS) (Grimm et al, 2011b), GD3 synthase (GD3S) (Grimm et al, 2012), Stathmin1 (Muller et al, 2013), and PGC1α (Robinson et al, 2013). A summary of these genes including the experimental procedures to investigate a potential impact of AICD on their expression are listed in Table 2.…”

Section: Aicd Nuclear Signaling and Its Impact On The Regulation Of Nepmentioning

confidence: 99%

Neprilysin and Aβ Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer’s Disease

Grimm

Mett

Stahlmann

et al. 2013

Front. Aging Neurosci.

125

105

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One of the characteristic hallmarks of Alzheimer’s disease (AD) is an accumulation of amyloid β (Aβ) leading to plaque formation and toxic oligomeric Aβ complexes. Besides the de novo synthesis of Aβ caused by amyloidogenic processing of the amyloid precursor protein (APP), Aβ levels are also highly dependent on Aβ degradation. Several enzymes are described to cleave Aβ. In this review we focus on one of the most prominent Aβ degrading enzymes, the zinc-metalloprotease Neprilysin (NEP). In the first part of the review we discuss beside the general role of NEP in Aβ degradation the alterations of the enzyme observed during normal aging and the progression of AD. In vivo and cell culture experiments reveal that a decreased NEP level results in an increased Aβ level and vice versa. In a pathological situation like AD, it has been reported that NEP levels and activity are decreased and it has been suggested that certain polymorphisms in the NEP gene result in an increased risk for AD. Conversely, increasing NEP activity in AD mouse models revealed an improvement in some behavioral tests. Therefore it has been suggested that increasing NEP might be an interesting potential target to treat or to be protective for AD making it indispensable to understand the regulation of NEP. Interestingly, it is discussed that the APP intracellular domain (AICD), one of the cleavage products of APP processing, which has high similarities to Notch receptor processing, might be involved in the transcriptional regulation of NEP. However, the mechanisms of NEP regulation by AICD, which might be helpful to develop new therapeutic strategies, are up to now controversially discussed and summarized in the second part of this review. In addition, we review the impact of AICD not only in the transcriptional regulation of NEP but also of further genes.

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Section: Aicd Nuclear Signaling and Its Impact On The Regulation Of Nepmentioning

confidence: 99%

Neprilysin and Aβ Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer’s Disease

Grimm

Mett

Stahlmann

et al. 2013

Front. Aging Neurosci.

125

105

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“…APP has been extensively studied in recent decades. Overall, a complex network of interactions with both extracellular and intracellular proteins has emerged (Müller et al, 2013). Several roles for AICD have been described, including its interaction with more than 20 cellular proteins.…”

Section: Discussionmentioning

confidence: 99%

Amyloid Precursor Protein (APP) Affects Global Protein Synthesis in Dividing Human Cells

Sobol¹,

Galluzzo²,

Liang³

et al. 2015

Journal Cellular Physiology

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Hypoxic non‐small cell lung cancer (NSCLC) is dependent on Notch‐1 signaling for survival. Targeting Notch‐1 by means of γ‐secretase inhibitors (GSI) proved effective in killing hypoxic NSCLC. Post‐mortem analysis of GSI‐treated, NSCLC‐burdened mice suggested enhanced phosphorylation of 4E‐BP1 at threonines 37/46 in hypoxic tumor tissues. In vitro dissection of this phenomenon revealed that Amyloid Precursor Protein (APP) inhibition was responsible for a non‐canonical 4E‐BP1 phosphorylation pattern rearrangement—a process, in part, mediated by APP regulation of the pseudophosphatase Styx. Upon APP depletion we observed modifications of eIF‐4F composition indicating increased recruitment of eIF‐4A to the mRNA cap. This phenomenon was supported by the observation that cells with depleted APP were partially resistant to silvestrol, an antibiotic that interferes with eIF‐4A assembly into eIF‐4F complexes. APP downregulation in dividing human cells increased the rate of global protein synthesis, both cap‐ and IRES‐dependent. Such an increase seemed independent of mTOR inhibition. After administration of Torin‐1, APP downregulation and Mechanistic Target of Rapamycin Complex 1 (mTORC‐1) inhibition affected 4E‐BP1 phosphorylation and global protein synthesis in opposite fashions. Additional investigations indicated that APP operates independently of mTORC‐1. Key phenomena described in this study were reversed by overexpression of the APP C‐terminal domain. The presented data suggest that APP may be a novel regulator of protein synthesis in dividing human cells, both cancerous and primary. Furthermore, APP appears to affect translation initiation using mechanisms seemingly dissimilar to mTORC‐1 regulation of cap‐dependent protein synthesis. J. Cell. Physiol. 230: 1064–1074, 2015. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

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“…; Müller et al . ). Hence, APP mediates epigenetic control of a number of genes at least in part through displacement of histone deacetylases (HDAC) (Belyaev et al .…”

Section: App Function Isoforms and Epigenetic Regulationmentioning

confidence: 97%

From synaptic spines to nuclear signaling: nuclear and synaptic actions of the amyloid precursor protein

Octave

Pierrot

Santos

et al. 2013

Journal of Neurochemistry

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Despite intensive studies of the secretase-mediated processing of the amyloid precursor protein (APP) to form the amyloid b-peptide (Ab), in relation to Alzheimer's disease (AD), no new therapeutic agents have reached the clinics based on reducing Ab levels through the use of secretase inhibitors or immunotherapy. Furthermore, the normal neuronal functions of APP and its various metabolites still remain under-investigated and unclear. Here, we highlight emerging areas of APP function that may provide new insights into synaptic development, cognition, and gene regulation. By modulating expression levels of endogenous APP in primary cortical neurons, the frequency and amplitude of calcium oscillations is modified, implying a key role for APP in maintaining neuronal calcium homeostasis essential for synaptic transmission.Disruption of this homeostatic mechanism predisposes to aging and AD. Synaptic spine loss is a feature of neurogeneration resulting in learning and memory deficits, and emerging evidence indicates a role for APP, probably mediated via one or more of its metabolites, in spine structure and functions. The intracellular domain of APP (AICD) has also emerged as a key epigenetic regulator of gene expression controlling a diverse range of genes, including APP itself, the amyloiddegrading enzyme neprilysin, and aquaporin-1. A fuller understanding of the physiological and pathological actions of APP and its metabolic network could provide new opportunities for therapeutic intervention in AD.

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A ternary complex consisting of AICD, FE65, and TIP60 down-regulates Stathmin1

Cited by 36 publications

References 47 publications

Neprilysin and Aβ Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer’s Disease

Neprilysin and Aβ Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer’s Disease

Amyloid Precursor Protein (APP) Affects Global Protein Synthesis in Dividing Human Cells

From synaptic spines to nuclear signaling: nuclear and synaptic actions of the amyloid precursor protein

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