14‐3‐3ζ Reduces DNA Damage by Interacting With and Stabilizing Proliferating Cell Nuclear Antigen

Gao, Xuejuan; Dan, Songsong; Xie, Yingying; Qin, Haixiang; Tang, Donge; Liu, Xiaohui; He, Qing-Yu; Liu, Langxia

doi:10.1002/jcb.24955

Cited by 16 publications

(21 citation statements)

References 48 publications

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“…Since our data showed that CUEDC2 protected LDHA from proteasome degradation without direct interaction with LDHA, we crossly compared the lists of candidate proteins binding to LDHA and the CUEDC2‐interacted ones, leading to the discovery of 14‐3‐3ζ as an effecter of CUEDC2 in regulation of LDHA protein stability. 14‐3‐3 family proteins, constituted of seven conserved members in eukaryotic cells, are well known for promoting cell survival by binding to a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and transmembrane receptors . Our further results proved that 14‐3‐3ζ was the direct mediator of LDHA activation and metabolic reprogramming triggered by CUEDC2 in cancer cells.…”

Section: Discussionsupporting

confidence: 58%

CUE domain‐containing protein 2 promotes the Warburg effect and tumorigenesis

et al. 2017

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Cancer progression depends on cellular metabolic reprogramming as both direct and indirect consequence of oncogenic lesions; however, the underlying mechanisms are still poorly understood. Here, we report that CUEDC2 (CUE domain-containing protein 2) plays a vital role in facilitating aerobic glycolysis, or Warburg effect, in cancer cells. Mechanistically, we show that CUEDC2 upregulates the two key glycolytic proteins GLUT3 and LDHA via interacting with the glucocorticoid receptor (GR) or 14-3-3ζ, respectively. We further demonstrate that enhanced aerobic glycolysis is essential for the role of CUEDC2 to drive cancer progression. Moreover, using tissue microarray analysis, we show a correlation between the aberrant expression of CUEDC2, and GLUT3 and LDHA in clinical HCC samples, further demonstrating a link between CUEDC2 and the Warburg effect during cancer development. Taken together, our findings reveal a previously unappreciated function of CUEDC2 in cancer cell metabolism and tumorigenesis, illustrating how close oncogenic lesions are intertwined with metabolic alterations promoting cancer progression.

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Section: Discussionsupporting

confidence: 58%

CUE domain‐containing protein 2 promotes the Warburg effect and tumorigenesis

et al. 2017

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“…A close association exists between PCNA and DNA synthesis (40). PCNA is also important for the initiation of cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Matrine reduces the proliferation of A549 cells via the p53/p21/PCNA/eIF4E signaling pathway

Xiao

Liu

et al. 2017

Molecular Medicine Reports

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The aim of the present study was to investigate how matrine affects the proliferation of A549 human lung adenocarcinoma cells via the p53/p21/proliferating cell nuclear antigen (PCNA)/eukaryotic translation initiation factor 4E (eIF4E) signaling pathway. The effect of different concentrations of matrine on the proliferation of A549 cells was investigated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The migration of A549 cells following exposure to varied concentrations of matrine was detected using a Transwell cell migration assay. The effect of 240 mg/l matrine on the apoptotic rate of A549 cells was determined using flow cytometry. The change in the mRNA and protein expression levels of p53, p21, PCNA and eIF4E following exposure to matrine were detected using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The increase of matrine from 60–240 mg/l led to reduced cell migration and inhibition of A549 cell proliferation. The apoptotic rate of A549 cells when treated with 240 mg/l matrine was significantly different when compared with the untreated control. The mRNA expression levels of p53 and p21 in the group treated with 240 mg/l matrine were significantly higher compared with the control group. The mRNA expression levels of PCNA and eIF4E were significantly lower in the 240 mg/l matrine-treated group compared with the control. The protein expression levels of p53 and p21 were significantly higher in the 240 mg/l matrine group compared with the control group. Treatment with 240 mg/l matrine reduced the protein expression levels of PCNA and eIF4E. Matrine also reduced the migration ability of A549 cells and inhibited their proliferation, which may be associated with the overexpression of p53 and p21, and the reduction of PCNA and eIF4E expression levels.

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“…The GST pull-down assays were performed as described previously 34 60 61 . Briefly, 1.5 mg whole cell lysate protein was incubated with 60 μg GST-hnRNPK protein overnight at 4 °C on a rocker.…”

Section: Methodsmentioning

confidence: 99%

hnRNPK inhibits GSK3β Ser9 phosphorylation, thereby stabilizing c-FLIP and contributes to TRAIL resistance in H1299 lung adenocarcinoma cells

Gao

Feng

et al. 2016

Sci Rep

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c-FLIP (cellular FLICE-inhibitory protein) is the pivotal regulator of TRAIL resistance in cancer cells, It is a short-lived protein degraded through the ubiquitin/proteasome pathway. The discovery of factors and mechanisms regulating its protein stability is important for the comprehension of TRAIL resistance by tumor cells. In this study, we show that, when H1299 lung adenocarcinoma cells are treated with TRAIL, hnRNPK is translocated from nucleus to cytoplasm where it interacts and co-localizes with GSK3β. We find that hnRNPK is able to inhibit the Ser9 phosphorylation of GSK3β by PKC. This has the effect of activating GSK3β and thereby stabilizing c-FLIP protein which contributes to the resistance to TRAIL in H1299 cells. Our immunohistochemical analysis using tissue microarray provides the clinical evidence of this finding by establishing a negative correlation between the level of hnRNPK expression and the Ser9 phosphorylation of GSK3β in both lung adenocarcinoma tissues and normal tissues. Moreover, in all cancer tissues examined, hnRNPK was found in the cytoplasm whereas it is exclusively nuclear in the normal tissues. Our study sheds new insights on the molecular mechanisms governing the resistance to TRAIL in tumor cells, and provides new clues for the combinatorial chemotherapeutic interventions with TRAIL.

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14‐3‐3ζ Reduces DNA Damage by Interacting With and Stabilizing Proliferating Cell Nuclear Antigen

Cited by 16 publications

References 48 publications

CUE domain‐containing protein 2 promotes the Warburg effect and tumorigenesis

CUE domain‐containing protein 2 promotes the Warburg effect and tumorigenesis

Matrine reduces the proliferation of A549 cells via the p53/p21/PCNA/eIF4E signaling pathway

hnRNPK inhibits GSK3β Ser9 phosphorylation, thereby stabilizing c-FLIP and contributes to TRAIL resistance in H1299 lung adenocarcinoma cells

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