Malignant H1299 tumour cells preferentially internalize iron-bound inositol hexakisphosphate

Helmis, Christina; Lin, Hongying; Schweizer, Michaela; Mayr, Georg W.; Nielsen, Peter; Windhorst, Sabine

doi:10.1042/bsr20130079

Cited by 4 publications

(2 citation statements)

References 17 publications

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“…Further studies from other laboratories have shown that lower concentrations of InsP 6 promoted cell proliferation, while higher concentrations led to induction of apoptosis Helmis et al 2013). Thus, a steady-state distribution of InsPs is the manifestation of a highly dynamic program of production and turnover by Minpp1 and other enzymes that regulate inositol polyphosphate inter-conversion which impact cell survival and death.…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum stress-induced apoptosis accompanies enhanced expression of multiple inositol polyphosphate phosphatase 1 (Minpp1): a possible role for Minpp1 in cellular stress response

Kilaparty

Agarwal

Singh

et al. 2016

Cell Stress and Chaperones

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Inositol polyphosphates represent a group of differentially phosphorylated inositol metabolites, many of which are implicated to regulate diverse cellular processes such as calcium mobilization, vesicular trafficking, differentiation, apoptosis, etc. The metabolic network of these compounds is complex and tightly regulated by various kinases and phosphatases present predominantly in the cytosol. Multiple inositol polyphosphate phosphatase 1 (Minpp1) is the only known endoplasmic reticulum (ER) luminal enzyme that hydrolyzes various inositol polyphosphates in vitro as well as in vivo conditions. However, access of the Minpp1 to cytosolic substrates has not yet been demonstrated clearly and hence its physiological function. In this study, we examined a potential role for Minpp1 in ER stress-induced apoptosis. We generated a custom antibody and characterized its specificity to study the expression of Minpp1 protein in multiple mammalian cells under experimentally induced cellular stress conditions. Our results demonstrate a significant increase in the expression of Minpp1 in response to a variety of cellular stress conditions. The protein expression was corroborated with the expression of its mRNA and enzymatic activity. Further, in an attempt to link the role of Minpp1 to apoptotic stress, we studied the effect of Minpp1 expression on apoptosis following silencing of the Minpp1 gene by its specific siRNA. Our results suggest an attenuation of apoptotic parameters following knockdown of Minpp1. Thus, in addition to its known role in inositol polyphosphate metabolism, we have identified a novel role for Minpp1 as a stress-responsive protein. In summary, our results provide, for the first time, a probable link between ER stress-induced apoptosis and Minpp1 expression.

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Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum stress-induced apoptosis accompanies enhanced expression of multiple inositol polyphosphate phosphatase 1 (Minpp1): a possible role for Minpp1 in cellular stress response

Kilaparty

Agarwal

Singh

et al. 2016

Cell Stress and Chaperones

View full text Add to dashboard Cite

show abstract

“…According to the literature, inositol polyphosphates (InsPs) were shown to play signaling roles in the regulation of calcium mobilization, cell growth, vesicular transport, gene expression, and export of mRNA and apoptosis [30][31][32][33][34]. MINPP1 is an ER luminal soluble protein and dephosphorylates InsPs by removing specifically phosphate group at position 3 and association with apoptosis has been described extensively [17,[35][36][37][38][39][40][41]. MINPP1 is the only ER resident enzyme that can hydrolyze inositol pentakisphosphate and inositol hexakisphosphate and it exhibits characteristics of a stress-responsive molecule during ER stress-induced apoptosis regardless of the underlying involved mechanisms [42].…”

Section: Discussionmentioning

confidence: 99%

Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1

et al. 2020

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Pontocerebellar hypoplasia (PCH) describes a group of rare heterogeneous neurodegenerative diseases with prenatal onset. Here we describe eight children with PCH from four unrelated families harboring the homozygous MINPP1 (NM_004897.4) variants; c.75_94del, p.(Leu27Argfs*39), c.851 C > A, p.(Ala284Asp), c.1210 C > T, p.(Arg404*), and c.992 T > G, p.(Ile331Ser). The homozygous p.(Leu27Argfs*39) change is predicted to result in a complete absence of MINPP1. The p.(Arg404*) would likely lead to a nonsense mediated decay, or alternatively, a loss of several secondary structure elements impairing protein folding. The missense p.(Ala284Asp) affects a buried, hydrophobic residue within the globular domain. The introduction of aspartic acid is energetically highly unfavorable and therefore predicted to cause a significant reduction in protein stability. The missense p.(Ile331Ser) affects the tight hydrophobic interactions of the isoleucine by the disruption of the polar side chain of serine, destabilizing the structure of MINPP1. The overlap of the above-mentioned genotypes and phenotypes is highly improbable by chance. MINPP1 is the only enzyme that hydrolyses inositol phosphates in the endoplasmic reticulum lumen and several studies support its role in stress induced apoptosis. The pathomechanism explaining the disease mechanism remains unknown, however several others genes of the inositol phosphatase metabolism (e.g., INPP5K, FIG4, INPP5E, ITPR1) are correlated with phenotypes of neurodevelopmental disorders. Taken together, we present MINPP1 as a novel autosomal recessive pontocerebellar hypoplasia gene.

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Regulatory roles of OASL in lung cancer cell sensitivity to Actinidia chinensis Planch root extract (acRoots)

Wang

Shen

et al. 2018

Cell Biol Toxicol

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Lung cancer is one of the most common malignancies worldwide. Actinidia chinensis Planch root extract (acRoots) was found to have the capacity of the anti-tumor, although the molecular mechanisms remain unclear. The present study aims to investigate the molecular mechanisms by which lung cancer cells sense to inhibitory effects of acRoots with a special focus on immune-associated gene profiles. We firstly provide a preclinical evidence that acRoots can significantly inhibit lung cancer cell proliferation and apoptosis via the PI3K-OASL signal pathway. The heterogeneous alterations of immune-associated gene profiles of lung cancer cell types were measured after treatment with various doses of acRoots. The OASL gene was identified as the key regulator in molecular networks of acRoots-treated lung cancer cells and validated. The OASL gene plays an important role in the regulation of lung cancer cell sensitivity to acRoots, which modulated by the PI3K signal pathway. Thus, our data indicate that OASL can be one of the decisive regulators to maintain lung cancer cell susceptibility to acRoots and may be associated with the development of drug resistance. The regulation of OASL can be an alternative strategy to improve drug efficacy during cancer therapies.

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Malignant H1299 tumour cells preferentially internalize iron-bound inositol hexakisphosphate

Cited by 4 publications

References 17 publications

Endoplasmic reticulum stress-induced apoptosis accompanies enhanced expression of multiple inositol polyphosphate phosphatase 1 (Minpp1): a possible role for Minpp1 in cellular stress response

Endoplasmic reticulum stress-induced apoptosis accompanies enhanced expression of multiple inositol polyphosphate phosphatase 1 (Minpp1): a possible role for Minpp1 in cellular stress response

Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1

Regulatory roles of OASL in lung cancer cell sensitivity to Actinidia chinensis Planch root extract (acRoots)

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