New Insights into Protein Kinase B/Akt Signaling: Role of Localized Akt Activation and Compartment-Specific Target Proteins for the Cellular Radiation Response

Szymonowicz, Klaudia; Oeck, Sebastian; Malewicz, Nathalie M.; Jendrossek, Verena

doi:10.3390/cancers10030078

Cited by 96 publications

(86 citation statements)

References 260 publications

(401 reference statements)

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“…Our observations are in consonant with earlier report on radiation‐induced reduction in PI3KCA mRNA and protein levels in laryngeal cancer . It has also been reported that radiation‐induced DNA damage promotes expression of Akt which further promotes radioresistance in cancer cells ; and therefore, its reduction could facilitate radiosensitivity in the cancer cells as shown by our data (Figs. a, d, e, and h).…”

Section: Discussionsupporting

confidence: 93%

Vicenin‐2 acts as a radiosensitizer of the non‐small cell lung cancer by lowering Akt expression

Baruah

Kma

2018

BioFactors

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Non‐small cell lung cancer (NSCLC) has a very high rate of incidence and is resistant to chemo‐ and radiotherapy. Vicenin‐2 (VCN‐2) is a flavonoid obtained from Ocimum sanctum L. and it has been reported to have radioprotective, anticancer, and radiosensitizing properties. We have conducted this study to check the effect of VCN‐2 on the cell viability and the effect on PTEN (Phosphatase and tensin homolog), PI3KCA (Phosphatidylinositol 4, 5‐biphosphate 3‐kinase catalytic subunit alpha isoform/PI3K 110α subunit), and Akt1 when VCN‐2 was used alone and in combination with radiation in the NSCLC cell line NCI‐H23 (H23). We have also checked the effect of VCN‐2 on various pro‐ and anti‐apoptotic genes and the ultra‐morphological changes that occurred in the cells when VCN‐2 is used alone and in combination with radiation. VCN‐2 was able to lower cancer cell survival and phosphorylated Akt while promoting the expression of pro‐apoptotic genes and down‐regulating anti‐apoptotic genes. We also observed the apoptosis‐associated ultra‐morphological changes in the VCN‐2‐treated cells. Our study have demonstrated that VCN‐2 can be a potential chemotherapeutic and radiosensitizing agent in NSCLC. © 2018 BioFactors, 45(2):200–210, 2019

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Section: Discussionsupporting

confidence: 93%

Vicenin‐2 acts as a radiosensitizer of the non‐small cell lung cancer by lowering Akt expression

Baruah

Kma

2018

BioFactors

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“…As the main molecule downstream of the PI3K signalling pathway, the serine/threonine protein kinase AKT comprises three subtypes, AKT1, AKT2 and AKT3, which are encoded by PKBα, PKBβ and PKBγ, respectively [3,21]. AKT1 is widely expressed in many tissues, AKT2 is expressed in mainly insulin-sensitive tissues and at low levels in other tissues, and AKT3 is expressed in only the brain and testis.…”

Section: Aktmentioning

confidence: 99%

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

et al. 2020

Cell Biosci

434

260

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The PI3 K/AKT/mTOR signalling pathway plays an important role in the regulation of signal transduction and biological processes such as cell proliferation, apoptosis, metabolism and angiogenesis. Compared with those of other signalling pathways, the components of the PI3K/AKT/mTOR signalling pathway are complicated. The regulatory mechanisms and biological functions of the PI3K/AKT/mTOR signalling pathway are important in many human diseases, including ischaemic brain injury, neurodegenerative diseases, and tumours. PI3K/AKT/mTOR signalling pathway inhibitors include single-component and dual inhibitors. Numerous PI3K inhibitors have exhibited good results in preclinical studies, and some have been clinically tested in haematologic malignancies and solid tumours. In this review, we briefly summarize the results of research on the PI3K/AKT/mTOR pathway and discuss the structural composition, activation, communication processes, regulatory mechanisms and biological functions of the PI3K/AKT/mTOR signalling pathway in the pathogenesis of neurodegenerative diseases and tumours.

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“…AKT has been implicated in regulating diverse substrates that have nuclear functions, including important roles in gene expression, DDR, DNA repair, and the maintenance of genomic stability (Szymonowicz et al, 2018). For example, activated AKT in the nucleus (immediately after Ser473 phosphorylation by DNA-PK) may conceivably regulate phosphorylation of the transcription factor FOXO, which resides in the nucleus prior to AKT phosphorylation (Brunet et al, 1999;Brunet et al, 2002), or DNA repair effector proteins, such as XLF or MERIT40 (Brown et al, 2015;Liu et al, 2015).…”

Section: Akt Dynamic Localization In Response To Nuclear Dna Damagementioning

confidence: 99%

Topoisomerase 2β-dependent nuclear DNA damage shapes extracellular growth factor responses through AKT phosphorylation dynamics to control virus latency

Shiflett

Kobayashi

et al. 2019

Preprint

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Running title: Control of viral latency by the DNA damage response SUMMARY The mTOR pathway integrates both extracellular and intracellular signals and serves as a central regulator of cell metabolism, growth, survival and stress responses. Neurotropic viruses, such as herpes simplex virus-1 (HSV-1), also rely on cellular AKT-mTORC1 signaling to achieve viral latency. Here, we define a novel genotoxic response whereby spatially separated signals initiated by extracellular neurotrophic factors and nuclear DNA damage are integrated by the AKT-mTORC1 pathway. We demonstrate that endogenous DNA double-strand breaks (DSBs) mediated by Topoisomerase 2b-DNA cleavage complex (TOP2bcc) intermediates are required to achieve AKT-mTORC1 signaling and maintain HSV-1 latency in neurons. Suppression of host DNA repair pathways that remove TOP2bcc trigger HSV-1 reactivation. Moreover, perturbation of AKT phosphorylation dynamics by downregulating the PHLPP1 phosphatase led to AKT mislocalization and disruption of DSB-induced HSV-1 reactivation. Thus, the cellular genome integrity and environmental inputs are consolidated and co-opted by a latent virus to balance lifelong infection with transmission.

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New Insights into Protein Kinase B/Akt Signaling: Role of Localized Akt Activation and Compartment-Specific Target Proteins for the Cellular Radiation Response

Cited by 96 publications

References 260 publications

Vicenin‐2 acts as a radiosensitizer of the non‐small cell lung cancer by lowering Akt expression

Vicenin‐2 acts as a radiosensitizer of the non‐small cell lung cancer by lowering Akt expression

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

Topoisomerase 2β-dependent nuclear DNA damage shapes extracellular growth factor responses through AKT phosphorylation dynamics to control virus latency

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