A tale of two clocks: phosphorylation of
            <scp>NICD</scp>
            by
            <scp>CDK</scp>
            s links cell cycle and segmentation clock

Braunreiter, Kara M.; Cole, Susan E.

doi:10.15252/embr.201948247

Cited by 4 publications

(5 citation statements)

References 14 publications

(29 reference statements)

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“…Afterwards, notch signaling is terminated by triggering ubiquitinated degradation of NICD PEST domain with the absence of SCF E3 ubiquitin ligase [53,54]. And the recognition of NICD by this ligase is mainly mediated by FBXW7, which binds to the phosphorylated NICD to recruit E3 ubiquitin ligase [55]. Mutations within the PEST domain of NICD or mutation of FBXW7 result in NICD stabilization, thereby leading to abnormal activation of its downstream targets [54][55][56].…”

Section: Discussionmentioning

confidence: 99%

“…And the recognition of NICD by this ligase is mainly mediated by FBXW7, which binds to the phosphorylated NICD to recruit E3 ubiquitin ligase [55]. Mutations within the PEST domain of NICD or mutation of FBXW7 result in NICD stabilization, thereby leading to abnormal activation of its downstream targets [54][55][56]. Accumulating evidence shows the phosphorylation of NICD enhances FBXW7 binding, indicating a potential mechanism to suppress notch signaling by NICD ubiquitination [54].…”

Section: Discussionmentioning

confidence: 99%

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Loss of PLK2 induces acquired resistance to temozolomide in GBM via activation of notch signaling

Wahafu

et al. 2020

J Exp Clin Cancer Res

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Background Glioblastoma (GBM) is a lethal type of primary brain tumor with a median survival less than 15 months. Despite the recent improvements of comprehensive strategies, the outcomes for GBM patients remain dismal. Accumulating evidence indicates that rapid acquired chemoresistance is the major cause of GBM recurrence thus leads to worse clinical outcomes. Therefore, developing novel biomarkers and therapeutic targets for chemoresistant GBM is crucial for long-term cures. Methods Transcriptomic profiles of glioblastoma were downloaded from gene expression omnibus (GEO) and TCGA database. Differentially expressed genes were analyzed and candidate gene PLK2 was selected for subsequent validation. Clinical samples and corresponding data were collected from our center and measured using immunohistochemistry analysis. Lentiviral transduction and in vivo xenograft transplantation were used to validate the bioinformatic findings. GSEA analyses were conducted to identify potential signaling pathways related to PLK2 expression and further confirmed by in vitro mechanistic assays. Results In this study, we identified PLK2 as an extremely suppressed kinase-encoding gene in GBM samples, particularly in therapy resistant GBM. Additionally, reduced PLK2 expression implied poor prognosis and TMZ resistance in GBM patients. Functionally, up-regulated PLK2 attenuated cell proliferation, migration, invasion, and tumorigenesis of GBM cells. Besides, exogenous overexpression of PLK2 reduced acquired TMZ resistance of GBM cells. Furthermore, bioinformatics analysis indicated that PLK2 was negatively correlated with Notch signaling pathway in GBM. Mechanically, loss of PLK2 activated Notch pathway through negative transcriptional regulation of HES1 and degradation of Notch1. Conclusion Loss of PLK2 enhances aggressive biological behavior of GBM through activation of Notch signaling, indicating that PLK2 could be a prognostic biomarker and potential therapeutic target for chemoresistant GBM.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Loss of PLK2 induces acquired resistance to temozolomide in GBM via activation of notch signaling

Wahafu

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…Afterwards, notch signaling is terminated by triggering ubiquitinated degradation of NICD PEST domain with the absence of SCF E3 ubiquitin ligase (50,51). And the recognition of NICD by this ligase is mainly mediated by FBXW7, which binds to the phosphorylated NICD to recruit E3 ubiquitin ligase (52). Mutations within the PEST domain of NICD or mutation of FBXW7 result in NICD stabilization, thereby leading to abnormal activation of its downstream targets (51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

“…And the recognition of NICD by this ligase is mainly mediated by FBXW7, which binds to the phosphorylated NICD to recruit E3 ubiquitin ligase (52). Mutations within the PEST domain of NICD or mutation of FBXW7 result in NICD stabilization, thereby leading to abnormal activation of its downstream targets (51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

Loss of PLK2 Induces Acquired Resistance to Temozolomide in GBM via Activation of Notch Signaling

Alafate

et al. 2020

Preprint

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BackgroundGlioblastoma (GBM) isa lethal type of primary brain tumor with a median survival less than 15 months.Despiting the recent improvements of comprehensive strategies,the outcomes for GBM patients remain dismal.Accumulating evidence indicates that rapid acquired chemoresistance is the major cause ofGBM recurrence thus leads to worse clinical outcomes. Therefore, developing novel biomarkers and therapeutic targets for chemoresistant GBM is crucial for long-term cures. MethodsTranscriptomic profiles of glioblastoma were downloaded from gene expression omnibus (GEO) and TCGA database. Differentially expressed genes were analyzed and candidate gene PLK2 was selected for subsequent validation. Clinical samples and corresponding data were collected from our center and measured using immunohistochemistry analysis. Lentiviral transduction and in vivo xenograft transplantation were used to validate the bioinformatic findings. GSEA analyses were conducted to identify potential signaling pathways related to PLK2 expression and further confirmed by in vitro mechanistic assays. ResultsIn this study, we identified PLK2 as an extremely suppressed kinase-encoding gene in GBM samples, particularly in therapy resistant GBM. Additionally, reduced PLK2 expression implied poor prognosis and TMZ resistance in GBM patients. Functionally, up-regulated PLK2 attenuated cell proliferation, immigration, invasion, and tumorigenesis of GBM cells. Besides, exogenous overexpression of PLK2 reduced acquired TMZ resistance of GBM cells. Furthermore, bioinformatics analysis indicated that PLK2 was negatively correlated with Notch signaling pathway in GBM. Mechanically, loss of PLK2 activated Notch pathway through negative transcriptional regulation of HES1 and degradation of Notch1.ConclusionLoss of PLK2 enhances aggressive biological behavior of GBM through activation of Notch signaling, indicating that PLK2 could be a prognostic biomarker and potential therapeutic target for chemoresistant GBM.

show abstract

“…And the recognition of NICD by this ligase is mainly mediated by FBXW7, which binds to the phosphorylated NICD to recruit E3 ubiquitin ligase (55). Mutations within the PEST domain of NICD or mutation of FBXW7 result in NICD stabilization, thereby leading to abnormal activation of its downstream targets (54)(55)(56).…”

Section: Discussionmentioning

confidence: 99%

Loss of PLK2 induces acquired resistance to temozolomide in GBM via activation of Notch signaling

Alafate

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundGlioblastoma (GBM) is a lethal type of primary brain tumor with a median survival less than 15 months. Despite the recent improvements of comprehensive strategies, the outcomes for GBM patients remain dismal. Accumulating evidence indicates that rapid acquired chemoresistance is the major cause of GBM recurrence thus leads to worse clinical outcomes. Therefore, developing novel biomarkers and therapeutic targets for chemoresistant GBM is crucial for long-term cures. MethodsTranscriptomic profiles of glioblastoma were downloaded from gene expression omnibus (GEO) and TCGA database. Differentially expressed genes were analyzed and candidate gene PLK2 was selected for subsequent validation. Clinical samples and corresponding data were collected from our center and measured using immunohistochemistry analysis. Lentiviral transduction and in vivo xenograft transplantation were used to validate the bioinformatic findings. GSEA analyses were conducted to identify potential signaling pathways related to PLK2 expression and further confirmed by in vitro mechanistic assays. ResultsIn this study, we identified PLK2 as an extremely suppressed kinase-encoding gene in GBM samples, particularly in therapy resistant GBM. Additionally, reduced PLK2 expression implied poor prognosis and TMZ resistance in GBM patients. Functionally, up-regulated PLK2 attenuated cell proliferation, migration, invasion, and tumorigenesis of GBM cells. Besides, exogenous overexpression of PLK2 reduced acquired TMZ resistance of GBM cells. Furthermore, bioinformatics analysis indicated that PLK2 was negatively correlated with Notch signaling pathway in GBM. Mechanically, loss of PLK2 activated Notch pathway through negative transcriptional regulation of HES1 and degradation of Notch1.ConclusionLoss of PLK2 enhances aggressive biological behavior of GBM through activation of Notch signaling, indicating that PLK2 could be a prognostic biomarker and potential therapeutic target for chemoresistant GBM.

show abstract

A tale of two clocks: phosphorylation of NICD by CDK s links cell cycle and segmentation clock

Cited by 4 publications

References 14 publications

Loss of PLK2 induces acquired resistance to temozolomide in GBM via activation of notch signaling

Loss of PLK2 induces acquired resistance to temozolomide in GBM via activation of notch signaling

Loss of PLK2 Induces Acquired Resistance to Temozolomide in GBM via Activation of Notch Signaling

Loss of PLK2 induces acquired resistance to temozolomide in GBM via activation of Notch signaling

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