PBK/TOPK interacts with the DBD domain of tumor suppressor p53 and modulates expression of transcriptional targets including p21

Hu, Fang; Rb, Gartenhaus; Eichberg, Daniel G.; Z, Liu; Hb, Fang; Ap, Rapoport

doi:10.1038/onc.2010.275

Cited by 110 publications

(124 citation statements)

References 42 publications

Supporting

Mentioning

118

Contrasting

Order By: Relevance

“…Moreover apoptotic cell analysis demonstrated that the down-regulation of PBK/TOPK increased early apoptosis (annexin Vpositive/PI-negative) and late apoptosis (annexin V/PI-double positive) 72 h after siRNA-PBK/TOPK transfection compared with transfection with control siRNA in mutant-type TP53 TE14 cells ( Figure 3B). This suggests that in tumors with wild-type TP53, p53 may be an important background for PBK/TOPK, as reported previously (15). In p53-mutant patients, however, it suggests that PBK/TOPK may contribute to tumorigenesis by suppressing apoptosis in a pathway different from the p53 pathway.…”

Section: Discussionmentioning

confidence: 52%

“…Most importantly, by impairing the DNA damage-induced apoptotic pathway, that is the p53 pathway, PBK/TOPK prevents cancer cell death (13). PBK/TOPK physically interacts with p53, specifically through its DNA-binding domain and promotes tumor cell survival and resistance to chemotherapy-induced apoptosis through suppression of p21 (15 us to clarify the clinicopathological and independent prognostic significance of PBK/TOPK overexpression/ activation through the p53 pathways in primary ESCC. Here, we hypothesized that overexpression/activation of PBK/TOPK may promote tumor cell proliferation and lead to poor survival of patients with ESCC.…”

Section: Discussionmentioning

confidence: 99%

“…PBK/TOPK was initially identified as a mitotic protein kinase (27), assisting the recruitment of cylcin-dependent kinase 1 (CDK1)/cyclin B to mitotic spindles, where PBK/TOPK plays a role in the formation of the spindle midzone and cytokinesis (10). Previous studies have identified various oncogenic functions of PBK/TOPK related to multiple signaling pathways such as the MAPK pathway (14), PI3K/AKT pathway (8,28,29) and p53 pathway (13,15). Through the MAPK pathway, PBK/TOPK functions as mediator of growth-factor activation of p38, with a role in motility and as part of the DNA damage sensing machinery, and is necessary for the phosphorylation of histone H2AX (14).…”

Section: Discussionmentioning

confidence: 99%

“…PBK/TOPK gene expression is regulated by the cell-cycle-specific transcription factors E2F and cAMPresponsive element binding/activating transcription factor (CREB/ATF) (12). PBK/TOPK prevents cancer cell death by impairing processes in the DNA damage-induced apoptosis pathway (13)(14)(15), such as tumor suppressor p53 and p38-mitogen-activated protein kinase (p38-MAPK) activities. PBK/TOPK promotes cell migration by modulating phosphoinositide 3-kinase/phosphatase and tensin homolog/ AKT (PI3K/PTEN/AKT)-dependent signaling (8).…”

Section: Overexpression Of Pbk/topk Contributes To Tumor Development mentioning

confidence: 99%

See 3 more Smart Citations

Overexpression of PBK/TOPK Contributes to Tumor Development and Poor Outcome of Esophageal Squamous Cell Carcinoma

Ohashi

Komatsu

Ichikawa

et al. 2016

View full text Add to dashboard Cite

Abstract. Background: PDZ-binding kinase/T-celloriginated protein kinase (PBK/TOPK) is a serine-threonine kinase and overexpressed in various types of cancer. PBK/TOPK is associated with tumor cell development and 58). Knockdown of PBK/TOPK using specific siRNAs inhibited the cell proliferation, invasion/migration of PBK/TOPK-overexpressing ESCC cell lines. Conclusion: These findings suggest that PBK/TOPK plays a crucial role in tumor malignant potential through its overexpression in ESCC.Esophageal cancer is the eighth most common cancer in the world (1) and esophageal squamous cell carcinoma (ESCC) accounts for 90% of esophageal carcinomas diagnosed in Asian countries. Although surgical techniques and perioperative management have progressed, ESCC remains one of the most aggressive carcinomas of the gastrointestinal tract. Since finding molecular targets for ESCC treatment might help improve the survival of patients with this lethal disease, studies have attempted to identify biological factors involved in the malignant potential of ESCC. However, few genes have been demonstrated to be associated with biological or pathological features of ESCC, suggesting that novel genes associated with the progression of ESCC need to be identified.Because identifying molecular targets for ESCC treatment may contribute to the improvement of survival of patients with this lethal disease, several recent studies have clarified that certain molecules, such as cyclo-oxygenase 2 (COX2), B-cell lymphoma (BCL2), tumor protein P53 (TP53), p16, cyclin D1, FAS, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and E-cadherin (2-6), have important roles in tumorigenesis and the development of ESCC. Moreover, various genetic and epigenetic alterations that contribute to the carcinogenesis of ESCC have been elucidated. In clinical settings, however, only a few molecules have been validated as diagnostic, therapeutic, or prognostic biomarkers for ESCC. These findings prompted us to further search for novel cancerassociated molecules.PDZ binding kinase/T-LAK cell originated protein kinase (PBK/TOPK) encodes a serine/threonine protein kinase and is 6457

show abstract

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Overexpression Of Pbk/topk Contributes To Tumor Development mentioning

confidence: 99%

See 2 more Smart Citations

Overexpression of PBK/TOPK Contributes to Tumor Development and Poor Outcome of Esophageal Squamous Cell Carcinoma

Ohashi

Komatsu

Ichikawa

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Recently, TOPK has been identified as a downstream target of the EWS-FLI chimeric fusion protein, which has a significant role in Ewing sarcoma biology (Herrero-Martin et al, 2009). Furthermore, TOPK physically interacts with p53 and may contribute to tumorigenesis through the suppression of p53 function (Nandi et al, 2007;Hu et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer

et al. 2011

View full text Add to dashboard Cite

We integrated four gene expression profile data sets, namely two different pair-matched stage I lung adenocarcinoma data sets, secondary metastatic tumors vs benign tumors and lung tumor metastasizes to the brain, and we identified one kinase, T-LAK Cell-Originated Protein Kinase (TOPK), as a putative gene that promotes metastasis. To delineate the role of TOPK in lung cancer, we showed that overexpression of TOPK, but not a catalytically inactive form of TOPK, can enhance the migration and invasion of lung fibroblasts or cells with low TOPK expression. In addition, TOPK-induced cell migration was shown to be a PI3K/AKT-dependent event. TOPK concurrently promoted AKT phosphorylation at Ser 473 and decreased the phosphatase and tensin homolog (PTEN) levels, whereas TOPK knockdown had the reverse effects. LY294002, a PI3K inhibitor, did not inhibit the TOPK-induced decrease in PTEN, and coexpression of PTEN significantly reduced TOPK-induced AKT phosphorylation in a dose-dependent manner; these results indicate that the TOPK-mediated PTEN decrease has an upstream role in regulating PI3K/AKT-stimulated migration. Using immunohistochemical analysis of lung cancer tissue samples, we showed that a high TOPK expression level correlates strongly with reduced overall and disease-free survivals. Moreover, an inverse correlation between TOPK and PTEN expression was present and is consistent with the biochemical findings. Finally, a combination of high TOPK and low PTEN expression was inversely correlated with overall and disease-free survivals, independent of other pathologic staging factors. Our results suggest that TOPK is a potential therapeutic target in lung cancer that promotes cell migration by modulating a PI3K/PTEN/AKT-dependent signaling pathway; they also suggest that high TOPK expression, either alone or in combination with a low level of PTEN, may serve as a prognostic marker for lung cancer.

show abstract

PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cells

Park

Lee

et al. 2020

FEBS Open Bio

View full text Add to dashboard Cite

PDZ‐binding kinase (PBK) has previously been shown to mediate chemoresistance of cancer cells to anticancer drugs. However, it remains unclear how PBK regulates paclitaxel‐induced cancer cell death. Here, we demonstrate that PBK hinders paclitaxel‐mediated autophagic cell death in H460 non‐small‐cell lung cancer cells. PBK knockdown increased apoptosis, autophagy, p53 level, and LC3 puncta upon paclitaxel treatment. Moreover, p53 expression facilitated an increase in the LC3‐II/LC3‐I ratio in response to paclitaxel, and PBK knockdown augmented paclitaxel‐mediated p53 transcriptional activity. Meanwhile, paclitaxel induced PBK‐mediated p53 nuclear export and its subsequent ubiquitination in control cells, but not in PBK knockdown cells. We conclude that PBK hampers paclitaxel‐induced autophagic cell death by suppressing p53, suggesting a potential role of PBK in p53‐mediated H460 cell death.

show abstract

PBK/TOPK interacts with the DBD domain of tumor suppressor p53 and modulates expression of transcriptional targets including p21

Cited by 110 publications

References 42 publications

Overexpression of PBK/TOPK Contributes to Tumor Development and Poor Outcome of Esophageal Squamous Cell Carcinoma

Overexpression of PBK/TOPK Contributes to Tumor Development and Poor Outcome of Esophageal Squamous Cell Carcinoma

TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer

PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cells

Contact Info

Product

Resources

About