Inositol hexakisphosphate kinases promote autophagy

Nagata, Eiichiro; Saiardi, Adolfo; Tsukamoto, Hideo; Satoh, Takahiro; Itoh, Yoshiko; Itoh, Johbu; Shibata, Mamoru; Takizawa, Shunya; Takagi, Shigeharu

doi:10.1016/j.biocel.2010.09.013

Cited by 30 publications

(35 citation statements)

References 37 publications

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“…We proposed previously that InsP 6 Ks might act through the synthesis of InsP 7 to induce caspase-independent cell death (14). We also observed an increase in the number of autophagosomes in InsP 6 K-activated cells.…”

Section: Discussionsupporting

confidence: 68%

“…We recently showed that InsP 6 Ks, particularly InsP 6 K2, regulate cell death and promote autophagy (14). During its activation process, InsP 6 K2 is translocated from the nucleus to the cytoplasm (5).…”

Section: Insp 6 K2 Exists In the Cytoplasm Of Hd Lymphoblast Cells-mentioning

confidence: 99%

“…We have previously reported that InsP 6 Ks promote autophagy (14), a cellular clearance mechanism that occurs in patients with Huntington disease (HD). Therefore, in this study, we investigated whether InsP 6 K signaling is activated in HD lymphoblast cells.…”

mentioning

confidence: 99%

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Inositol Hexakisphosphate Kinases Induce Cell Death in Huntington Disease

Nagata

Saiardi

Tsukamoto

et al. 2011

Journal of Biological Chemistry

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Inositol pyrophosphate diphosphoinositol pentakisphosphate is ubiquitously present in mammalian cells and contains highly energetic pyrophosphate bonds. We have previously reported that inositol hexakisphosphate kinase type 2 (InsP 6 K2), which converts inositol hexakisphosphate to inositol pyrophosphate diphosphoinositol pentakisphosphate, mediates apoptotic cell death via its translocation from the nucleus to the cytoplasm. Here, we report that InsP 6 K2 is localized mainly in the cytoplasm of lymphoblast cells from patients with Huntington disease (HD), whereas this enzyme is localized in the nucleus in control lymphoblast cells. The large number of autophagosomes detected in HD lymphoblast cells is consistent with the down-regulation of Akt in response to InsP 6 K2 activation. Consistent with these observations, the overexpression of InsP 6 Ks leads to the depletion of Akt phosphorylation and the induction of cell death. These results suggest that InsP 6 K2 activation is associated with the pathogenesis of HD.

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Section: Discussionsupporting

confidence: 68%

Section: Insp 6 K2 Exists In the Cytoplasm Of Hd Lymphoblast Cells-mentioning

confidence: 99%

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Inositol Hexakisphosphate Kinases Induce Cell Death in Huntington Disease

Nagata

Saiardi

Tsukamoto

et al. 2011

Journal of Biological Chemistry

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“…The autophagy-related genes encoding inositol hexakisphosphate kinase 1 (InsP6K1 [g615.t1]) and a cullin domain-containing protein (g11374.t1) were upregulated after harvest (Table S7). InsP6K forms diphosphoinositol pentakisphosphate [InsP (7)], which induces autophagy (67). Furthermore, InsP6K mediates the assembly/disassembly of the cullin-RING ubiquitin ligases (CRL)-signalosome complex to regulate cell death (68).…”

Section: Resultsmentioning

confidence: 99%

Lentinula edodes Genome Survey and Postharvest Transcriptome Analysis

Sakamoto

Nakade

Sato

et al. 2017

Appl Environ Microbiol

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Lentinula edodes is a popular, cultivated edible and medicinal mushroom. Lentinula edodes is susceptible to postharvest problems, such as gill browning, fruiting body softening, and lentinan degradation. We constructed a de novo assembly draft genome sequence and performed gene prediction for Lentinula edodes. De novo assembly was carried out using short reads from paired-end and mate-paired libraries and by using long reads by PacBio, resulting in a contig number of 1,951 and an N 50 of 1 Mb. Furthermore, we predicted genes by Augustus using transcriptome sequencing (RNA-seq) data from the whole life cycle of Lentinula edodes, resulting in 12,959 predicted genes. This analysis revealed that Lentinula edodes lacks lignin peroxidase. To reveal genes involved in the loss of quality of Lentinula edodes postharvest fruiting bodies, transcriptome analysis was carried out using serial analysis of gene expression (SuperSAGE). This analysis revealed that many cell wall-related enzymes are upregulated after harvest, such as ␤-1,3-1,6-glucan-degrading enzymes in glycoside hydrolase (GH) families GH5, GH16, GH30, GH55, and GH128, and thaumatin-like proteins. In addition, we found that several chitin-related genes are upregulated, such as putative chitinases in GH family 18, exochitinases in GH20, and a putative chitosanase in GH family 75. The results suggest that cell wall-degrading enzymes synergistically cooperate for rapid fruiting body autolysis. Many putative transcription factor genes were upregulated postharvest, such as genes containing high-mobility-group (HMG) domains and zinc finger domains. Several cell deathrelated proteins were also upregulated postharvest.IMPORTANCE Our data collectively suggest that there is a rapid fruiting body autolysis system in Lentinula edodes. The genes for the loss of postharvest quality newly found in this research will be targets for the future breeding of strains that keep fresh longer than present strains. De novo Lentinula edodes genome assembly data will be used for the construction of a complete Lentinula edodes chromosome map for future breeding.

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“…Overexpression of IP6Ks in mammalian cells led to an increase in the number of stress-induced autophagosomes as compared with control cells, and reduced expression of IP6Ks using RNA interference suppressed autophagosome formation. 94 Expression of an inactive IP6K had no effect, revealing that autophagosome formation is IP 7 dependent. The evolutionarily conserved protein kinase mTOR is a master regulator of cell growth and metabolism, and negatively regulates autophagy.…”

Section: Autophagymentioning

confidence: 98%

Inositol Pyrophosphates: Energetic, Omnipresent and Versatile Signalling Molecules

et al. 2017

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| Inositol pyrophosphates (PP-IPs) are a class of energy-rich signalling molecules found in all eukaryotic cells. These are derivatives of inositol that contain one or more diphosphate (or pyrophosphate) groups in addition to monophosphates. The more abundant and best studied PP-IPs are diphosphoinositol pentakisphosphate (IP 7 ) and bis-diphosphoinositol tetrakisphosphate (IP 8 ). These molecules can influence protein function by two mechanisms: binding and pyrophosphorylation. The former involves the specific interaction of a particular inositol pyrophosphate with a binding site on a protein, while the latter is a unique attribute of inositol pyrophosphates, wherein the β-phosphate moiety is transferred from a PP-IP to a pre-phosphorylated serine residue in a protein to generate pyrophosphoserine. Both these events can result in changes in the target protein's activity, localisation or its interaction with other partners. As a consequence of their ubiquitous presence in all eukaryotic organisms and all cell types examined till date, and their ability to modify protein function, PP-IPs have been found to participate in a wide range of metabolic, developmental, and signalling pathways.This review highlights many of the known functions of PP-IPs in the context of their temporal and spatial distribution in eukaryotic cells. The pathway of synthesis of inositol polyphosphates has been characterized in yeast, slime moulds, plants and animals. The simplest anabolic pathway, characterized in the yeast Saccharomyces cerevisiae (Fig. 1) (Fig. 1). Interestingly, the PPIP5Ks also possess a phosphatase domain which selectively cleaves the 1-position β-phosphate of 1-IP 7 and IP 8 , thus targeting the products of the kinase domain.35, 36 A recent study identified another yeast phosphatase, Siw14, that specifically targets the 5-position β-phosphate of PP-IPs 37 (Fig. 1). As PP-IPs are found in all eukaryotic organisms, they display many conserved and divergent 2, 131 Siw14, an inositol pyrophosphate phosphatase in yeast, preferentially cleaves the C5 β-phosphate on PP-IPs. 37 The yeast enzymes are depicted in purple, and mammalian enzymes are depicted in green and are bracketed. The undetermined inositol pyrophosphate structure is represented with an interrogation mark. Myoinositol contains five equatorial (parallel to the axis) and one axial (perpendicular to the axis) hydroxyl groups. Carbon atoms on the myo-inositol ring are numbered on the structures of PI(4,5)P 2 and IP 6 .

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Inositol hexakisphosphate kinases promote autophagy

Cited by 30 publications

References 37 publications

Inositol Hexakisphosphate Kinases Induce Cell Death in Huntington Disease

Inositol Hexakisphosphate Kinases Induce Cell Death in Huntington Disease

Lentinula edodes Genome Survey and Postharvest Transcriptome Analysis

Inositol Pyrophosphates: Energetic, Omnipresent and Versatile Signalling Molecules

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