Polo-like kinase 2 activates an antioxidant pathway to promote the survival of cells with mitochondrial dysfunction

Li, Jie; Ma, Wenzhe; Wang, Ping Yuan; Hurley, Paula J.; Bunz, Fred; Hwang, Paul M.

doi:10.1016/j.freeradbiomed.2014.05.022

Cited by 41 publications

(49 citation statements)

References 42 publications

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“…Homeostatic adaptation of the cell to external stress is mainly controlled by p53 target genes (37,38). A set of p53dependent genes such as Plk2 and p21 cip1 are activated by DNA damage, protecting cells from injury (25,(37)(38)(39)(40). Another set of p53-dependent genes such as BCL2 associated X (Bax), apoptosis regulator, P53 up-regulated modulator of apoptosis (Puma), and phorbol-12-myristate-13-acetate-induced protein 1 (Noxa) execute apoptosis (41).…”

Section: Discussionmentioning

confidence: 99%

Nrf2‐lncRNA controls cell fate by modulating p53‐dependent Nrf2 activation as an miRNA sponge for Plk2 and p21 ^cip1

et al. 2019

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Long noncoding RNA (lncRNA) capable of controlling antioxidative capacity remains to be investigated. Nuclear factor erythroid‐2–related factor 2 (Nrf2) is a central molecule for cellular defense that increases antioxidative capacity. We identified a novel lncRNA named Nrf2‐activating lncRNA (Nrf2‐lncRNA) transcribed from an upstream region of the microRNA 122 gene (MIR122). Nrf2‐lncRNA existed in the cytoplasm, suggestive of its function as a competing endogenous RNA [ceRNA, microRNA (miRNA) sponge]. Nrf2‐lncRNA served as a ceRNA for polo‐like kinase (Plk) 2 and cyclin‐dependent kinase inhibitor 1 (p21cip1) through binding of miRNA 128 and miRNA 224, inducing Plk2/Nrf2/p21cip1 complexation for Nrf2 activation in the cells under p53‐activating conditions (i.e., DNA damage and serum deprivation). Nrf2‐lncRNA expression was suppressed with the initiation of apoptosis, being a rheostat for cell fate determination. Nrf2‐lncRNA levels correlated with the recurrence‐free postsurgery survival rate of patients with hepatocellular carcinoma. Collectively, Nrf2‐lncRNA promotes Plk2 and p21cip1 translation by competing for specific miRNAs and activating Nrf2 under surviving conditions from oxidative stress, implying that Nrf2‐lncRNA serves as a fine‐tuning rheostat for cell fate decision.—Joo, M. S., Shin, S.‐B., Kim, E. J., Koo, J. H., Yim, H., Kim, S. G. Nrf2‐lncRNA controls cell fate by modulating p53‐dependent Nrf2 activation as an miRNA sponge for Plk2 and p21cip1. FASEB J. 33, 7953–7969 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Nrf2‐lncRNA controls cell fate by modulating p53‐dependent Nrf2 activation as an miRNA sponge for Plk2 and p21 ^cip1

et al. 2019

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“…Plk2, Plk3, and Plk5. Plks 2, 3, and 5 have been described as immediate early response genes since the expression of these three kinases increases upon DNA damage and oxidative stress [30][31][32][33][34][35]. This, in turn, leads to the activation of the G2/M checkpoint in a p53-dependent manner [36][37][38][39][40].…”

Section: The Plk Family: Expression Localization and Cellular Functmentioning

confidence: 99%

Polo-Like Kinases in Colorectal Cancer: Potential for Targeted Therapy

Kazazian

Brashavitskaya

Zih

et al. 2015

Curr Colorectal Cancer Rep

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The five individual members of the mammalian polo-like kinase family play non-redundant roles in centriole replication and maturation, mitotic progression, cytokinesis, and the DNA damage response. In human colorectal cancer, Plk1 and Plk4 are expressed at higher levels in tumor than adjacent normal mucosa, and the degree of overexpression correlates with adverse prognosis. In colorectal cancer cell lines, suppression of Plk1 activity leads to mitotic arrest and apoptosis, while inhibition of Plk4 activity reduces tumor growth and invasion. Inhibition of Plk1 or Plk4 in mice using orally bioavailable agents reduces the growth of human colorectal cancer xenografts. On the basis of these preclinical studies, clinical trials of several different targeted anti-Plk1 agents have been undertaken in patients with advanced solid tumors, and a phase I trial of the anti-Plk4 inhibitor CFI-400945 is currently accruing. Here, we review the rationale, results, and potential limitations of Plks as therapeutic targets. Evidence from genetic mouse models suggests that Plk1, Plk2, Plk3, and Plk4 may all possess tumor suppressive activity, particularly with aging. Thus, enthusiasm for the use of targeted Plk inhibitors in cancer therapy must be tempered somewhat by the potential for development of second primary tumors in the long term.

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“…We previously reported that PLK2 mediates defective mitochondrial changes and PLK2 activity is required for cell survival 20,21 . To investigate whether PLK2 is altered in DKD tissues, we performed the microarray and GSEA analysis.…”

Section: Resultsmentioning

confidence: 99%

PLK2 Plays an Essential Role in High D-Glucose-Induced Apoptosis, ROS Generation and Inflammation in Podocytes

Zou

Yang

Huang

et al. 2017

Sci Rep

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Diabetic kidney disease (DKD) is a serious complication of hyperglycemia. Currently, there is no effective therapeutic intervention for DKD. In this study, we sought to provide a set of gene profile in diabetic kidneys. We identified 338 genes altered in diabetes-induced DKD glomeruli, and PLK2 exhibited the most dramatic change. Gene set enrichment analysis (GSEA) indicated multiple signaling pathways are involved DKD pathogenesis. Here, we investigated whether PLK2 contributes to podocyte dysfunction, a characteristic change in the development of DKD. High D-glucose (HDG) significantly increased PLK2 expression in mouse podocytes. Suppressing PLK2 attenuated HDG-induced apoptosis and inflammatory responses both in vitro and in vivo. NAC, an antioxidant reagent, rescued HDG and PLK2 overexpression-induced kidney injuries. In summary, we demonstrated that silencing PLK2 attenuates HDG-induced podocyte apoptosis and inflammation, which may serve as a future therapeutic target in DKD.

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Polo-like kinase 2 activates an antioxidant pathway to promote the survival of cells with mitochondrial dysfunction

Cited by 41 publications

References 42 publications

Nrf2‐lncRNA controls cell fate by modulating p53‐dependent Nrf2 activation as an miRNA sponge for Plk2 and p21 ^cip1

Nrf2‐lncRNA controls cell fate by modulating p53‐dependent Nrf2 activation as an miRNA sponge for Plk2 and p21 ^cip1

Polo-Like Kinases in Colorectal Cancer: Potential for Targeted Therapy

PLK2 Plays an Essential Role in High D-Glucose-Induced Apoptosis, ROS Generation and Inflammation in Podocytes

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Polo-like kinase 2 activates an antioxidant pathway to promote the survival of cells with mitochondrial dysfunction

Cited by 41 publications

References 42 publications

Nrf2‐lncRNA controls cell fate by modulating p53‐dependent Nrf2 activation as an miRNA sponge for Plk2 and p21 cip1

Nrf2‐lncRNA controls cell fate by modulating p53‐dependent Nrf2 activation as an miRNA sponge for Plk2 and p21 cip1

Polo-Like Kinases in Colorectal Cancer: Potential for Targeted Therapy

PLK2 Plays an Essential Role in High D-Glucose-Induced Apoptosis, ROS Generation and Inflammation in Podocytes

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Nrf2‐lncRNA controls cell fate by modulating p53‐dependent Nrf2 activation as an miRNA sponge for Plk2 and p21 ^cip1

Nrf2‐lncRNA controls cell fate by modulating p53‐dependent Nrf2 activation as an miRNA sponge for Plk2 and p21 ^cip1