Correlation of intracellular diadenosine triphosphate (Ap3A) with apoptosis in Fhit-positive HEK293 cells

Fisher, David; McLennan, Alexander G.

doi:10.1016/j.canlet.2007.10.007

Cited by 21 publications

(49 citation statements)

References 30 publications

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“…Moreover, we showed that the dinucleotide diadenosine tetraphosphate (Ap 4 A), previously shown to be synthesized by LysRS, binds to Hint-1, and as a result the transcription factors are released from their suppression. Thus, transcriptional activity is regulated by Ap 4 A, suggesting that Ap 4 A is a second messenger in this context. For Ap 4 A to be unambiguously established as a second messenger, several criteria have to be fulfilled, including the presence of a metabolizing enzyme.…”

mentioning

confidence: 97%

“…Thus, transcriptional activity is regulated by Ap 4 A, suggesting that Ap 4 A is a second messenger in this context. For Ap 4 A to be unambiguously established as a second messenger, several criteria have to be fulfilled, including the presence of a metabolizing enzyme. Since several enzymes are able to hydrolize Ap 4 A, we provided here evidence that the "Nudix" type 2 gene product, Ap 4 The dinucleotide diadenosine tetraphosphate (Ap 4 A) is composed of two adenosine moieties joined in 5Ј-5Ј linkage by a chain of four phosphates.…”

mentioning

confidence: 97%

“…For Ap 4 A to be unambiguously established as a second messenger, several criteria have to be fulfilled, including the presence of a metabolizing enzyme. Since several enzymes are able to hydrolize Ap 4 A, we provided here evidence that the "Nudix" type 2 gene product, Ap 4 The dinucleotide diadenosine tetraphosphate (Ap 4 A) is composed of two adenosine moieties joined in 5Ј-5Ј linkage by a chain of four phosphates. As far as we know, Ap 4 A is found in all living cells, and ever since its discovery in 1966 (42), it has been proposed to be more than just a "toxic waste" substance (28).…”

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confidence: 99%

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Diadenosine Tetraphosphate Hydrolase Is Part of the Transcriptional Regulation Network in Immunologically Activated Mast Cells

Carmi-Levy

Yannay-Cohen

Kay

et al. 2008

Molecular and Cellular Biology

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confidence: 99%

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Diadenosine Tetraphosphate Hydrolase Is Part of the Transcriptional Regulation Network in Immunologically Activated Mast Cells

Carmi-Levy

Yannay-Cohen

Kay

et al. 2008

Molecular and Cellular Biology

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“…Several studies have illustrated a key role for HMOX1 in promoting cell survival during inflammation, and HMOX1 expression has multiple functions in smoking-mediated lung cancers. 20,[62][63][64][65] Because HMOX1 promotes cell proliferation and increases resistance to oxidative stress, overexpression of HMOX1 imparts a selective advantage to cells in the early stages of carcinogenesis and correlates with resistance to many chemotherapeutics in malignancy. 20,29,31,56 Thus, our data link loss of Fhit to a key pathway in the establishment and maintenance of the malignant state.…”

Section: Discussionmentioning

confidence: 99%

“…61 Indeed, the intracellular concentration of ApppA increases in cells exposed to oxidative stressors. [62][63][64][65] Because mutation of the Fhit enzyme active site histidine residue greatly retards ApppA cleavage without a strong effect on ApppA binding or proapoptotic activity After knockdown, cells were exposed to 1% CSE for 4 hours. Hmox1 protein abundance was assessed by western blot.…”

Section: Discussionmentioning

confidence: 99%

A knockdown with smoke model reveals FHIT as a repressor of Heme oxygenase 1

Boylston

Brenner²

2014

Cell Cycle

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Fragile histidine triad (FHIT) gene deletions are among the earliest and most frequent events in carcinogenesis, particularly in carcinogen-exposed tissues. Though FHIT has been established as an authentic tumor suppressor, the mechanism underlying tumor suppression remains opaque. Most experiments designed to clarify FHIT function have analyzed the consequence of re-expressing FHIT in FHIT-negative cells. However, carcinogenesis occurs in cells that transition from FHIT-positive to FHIT-negative. To better understand cancer development, we induced FHIT loss in human bronchial epithelial cells with RNA interference. Because FHIT is a demonstrated target of carcinogens in cigarette smoke, we combined FHIT silencing with cigarette smoke extract (CSE) exposure and measured gene expression consequences by RNA microarray. The data indicate that FHIT loss enhances the expression of a set of oxidative stress response genes after exposure to CSE, including the cytoprotective enzyme heme oxygenase 1 (HMOX1) at the RNA and protein levels. Data are consistent with a mechanism in which Fhit protein is required for accumulation of the transcriptional repressor of HMOX1, Bach1 protein. We posit that by allowing superinduction of oxidative stress response genes, loss of FHIT creates a survival advantage that promotes carcinogenesis.

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Das Alarmon Diadenosintetraphosphat als Cosubstrat für die AMPylierung von Proteinen

et al. 2023

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Diadenosinpolyphosphate (Ap n As) sind nicht-kanonische Nukleotide, deren zelluläre Konzentrationen bei Stress als Signal eines homöostatischen Ungleichgewichts ansteigen und die daher als Alarmone bezeichnet werden. Ihre zelluläre Rolle ist nur unzureichend verstanden. In dieser Arbeit haben wir untersucht, ob Ap n As als Cosubstrat für die AMPylierung von Proteinen verwendet werden. AMPylierung ist eine posttranslationale Modifikation, bei der Adenosinmonophosphat (AMP) auf Proteine übertragen wird. Beim Menschen ist die AMPylierung, die durch den AMPylator FICD mit ATP als Cosubstrat vermittelt wird, eine Reaktion auf ER-Stress. Hier zeigen wir, dass Ap 4 A für die AMPylierung durch FICD effizient verwendet wird. Durch chemische Proteomik unter Verwendung einer neuen chemischen Sonde haben wir neue potenzielle AMPylierungsziele identifiziert. Interessanterweise haben wir festgestellt, dass sich die AMPylierungsziele von FICD je nach Nukleotid-Cosubstrat unterscheiden können. Diese Ergebnisse könnten darauf hindeuten, dass sich die Signalübertragung bei erhöhten Ap 4 A-Spiegeln während zellulärem Stress von derjenigen bei niedrigen Ap 4 A Konzentrationen unterscheidet, und damit eine Reaktion auf extrazelluläre Signale ermöglicht.

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Correlation of intracellular diadenosine triphosphate (Ap3A) with apoptosis in Fhit-positive HEK293 cells

Cited by 21 publications

References 30 publications

Diadenosine Tetraphosphate Hydrolase Is Part of the Transcriptional Regulation Network in Immunologically Activated Mast Cells

Diadenosine Tetraphosphate Hydrolase Is Part of the Transcriptional Regulation Network in Immunologically Activated Mast Cells

A knockdown with smoke model reveals FHIT as a repressor of Heme oxygenase 1

Das Alarmon Diadenosintetraphosphat als Cosubstrat für die AMPylierung von Proteinen

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