p53 Modulation of DNA Topoisomerase IIα Gene Expression

Aa, Joshi; Wang, Q; Dp, Suttle

doi:10.1385/cbb:33:2:209

Cited by 4 publications

(3 citation statements)

References 36 publications

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“…For example, with incubation at 45ºC for 15 minutes, topo IIα mRNA rapidly degrades in HeLa cells (Goswami et al, 1996) but increases in human epidermoid cancer KB cells (Matsuo et al, 1993). The p53 protein is thought to be a negative regulator since studies overexpressing wild-type p53 demonstrated a decrease in topo IIα expression (Joshi et al, 2000;Sandri et al, 1996b). Inhibiting histone deacetylase in mouse embryonic fibroblasts (NIH3T3 cells) causes an ICB-dependent increase in topo IIα promoter activity, showing that histone deacetylation is important for down regulating topo IIα promoter activity (Adachi et al, 2000).…”

Section: Topo Iiα Protein Expressionmentioning

confidence: 99%

The effects of 1,4-benzoquinone on c-Myb and topoisomerase II in K-562 cells

Singh

Winn

2008

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Exposure to benzene, a ubiquitous environmental pollutant, has been linked to leukemia, although the mechanism of benzene-initiated leukemogenesis remains unclear. Benzene can be bioactivated to toxic metabolites such as 1,4 benzoquinone (BQ), which can alter signaling pathways and affect chromosomal integrity. BQ has been shown to increase the activity of c-Myb, which is an important transcription factor involved in hematopoiesis, cell proliferation, and cell differentiation. The c-Myb protein has also been shown to increase topoisomerase IIalpha (Topo IIalpha) promoter activity specifically in cell lines with hematopoietic origin. Topo IIalpha is a critical nuclear enzyme that removes torsional strain by cleaving, untangling and religating double-stranded DNA. Since Topo IIalpha mediates DNA strand breaks, aberrant Topo IIalpha activity or increased protein levels may increase the formation of DNA strand breaks, leaving the cell susceptible to mutational events. We hypothesized that BQ can increase c-Myb activity, which in turn increases Topo IIalpha promoter activity resulting in increased DNA strand breaks. Using luciferase reporter assays in K-562 cells we demonstrated that BQ (25 and 37microM) exposure caused an increase in c-Myb activity after 24h. Contradictory to previous findings, overexpression of exogenous c-Myb or a polypeptide consisting of c-Myb's DNA binding domain (DBD), which competitively inhibits the binding of endogenous c-Myb to DNA, did not affect Topo IIalpha promoter activity. However, BQ (37microM for 24h) exposure caused a significant increase in Topo IIalpha promoter activity, which could be blocked by the overexpression of the DBD polypeptide, suggesting that BQ exposure increases Topo IIalpha promoter activity through the c-Myb signaling pathway.

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Section: Topo Iiα Protein Expressionmentioning

confidence: 99%

The effects of 1,4-benzoquinone on c-Myb and topoisomerase II in K-562 cells

Singh

Winn

2008

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…18 The TOPO IIα promoter contains five inverted CCAAT boxes (ICB), several of which function as positive regulators of the promoter activity. [19][20][21] The most proximal element ICB1, however, appears to act as a negative regulatory site. Mutation of ICB1 does not diminish the TOPO IIα promoter function, but it interferes with the inhibition of this promoter during G1 22 or upon the expression of p53, the primary inducer of p21 in response to DNA damage.…”

Section: Introductionmentioning

confidence: 99%

Identification of Promoter Elements Responsible for Transcriptional Inhibition of Polo-like Kinase 1 and Topoisomerase IIα Genes by p21^{WAF1/CIP1/ SDI1}

Zhu¹,

Chang²,

Uchiumi³

et al. 2002

Cell Cycle

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© 2 0 0 2 L a n d e s B i o s c i e n c e . N o t f o r d i s t r i b u t i o n .[Cell Cycle 1, 59-66, January 2002]; published online as a Cell Cycle "Papers In Press" at www. ABSTRACT Induction of p21 WAF1/CIP1/SDI1 , a physiological mediator of cell cycle arrest, inhibits multiple genes involved in cell division. We have investigated the determinants of p21-mediated inhibition of two of these genes, polo-like kinase 1 (PLK1) and topoisomerase IIα (TOPO IIα). p21 expression from an inducible promoter in human HT1080 cells rapidly decreases cellular levels of PLK1 and TOPO IIα RNA without decreasing their RNA stability. p21 also inhibits reporter gene expression from the PLK1 and TOPO IIα promoters in transient and stable transfection assays. Promoter mutagenesis studies show that inhibition of the PLK1 promoter by p21 is mediated in part by tandem sequences CDE (cell cycle-dependent element) and CHR (cell cycle genes homology region). p21 response of the TOPO IIα promoter was found to be mediated through CDE (but not CHR) and the inverted CCAAT box 1 (ICB1). The extent of PLK1 and TOPO IIα promoter inhibition and the effects of promoter mutations differ under the conditions of growth arrest produced by p21 induction or by mimosine, a cell cycle inhibitor that increases p21 RNA but not protein expression in HT1080 cells. These results indicate that inhibition of cell division-associated genes by p21 is mediated by different but overlapping mechanisms, which are not a general consequence of cell cycle arrest.

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“…The tumour suppressor protein p53 is a transcription factor that both activates the expression of genes containing the p53 binding site and represses the expression of some genes that lack this binding site. 15 Previous studies have shown that overexpression of wild-type p53 leads to apoptosis and cell cycle arrest. 16 Mutations in the p53 gene occur very frequently in many human cancers.…”

Section: J Zhang X-h He X-y Xie Et Al P53 and Gastric Cancer Response To Chemotherapymentioning

confidence: 99%

The Potential for Serum p53 to Predict the Response to Chemotherapy of Patients with Gastric Cancer

Zhang

et al. 2010

J Int Med Res

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This study was designed to investigate the relationship between serum p53, tissue p53 and tissue permeability glycoprotein (P-gp) levels in gastric cancer. Serum levels of p53 were detected by enzyme-linked immunosorbent assay, and tissue p53 and P-gp levels were analysed by immunohistochemistry. In total, 63.0% of gastric cancer tissue samples tested positive for P-gp and 58.7% of samples tested positive for p53. Tissue P-gp immunoreactivity was significantly correlated with tissue p53 immunoreactivity, and both tissue p53 and P-gp immunoreactivity were significantly correlated to the degree of cancer cell differentiation. The percentage of gastric cancer patients with serum positive for p53 was 36.2%, which was significantly higher than the rate in non-cancerous gastric disease patients. Serum p53 was significantly correlated to tissue p53 and tissue P-gp, inferring that the presence of p53 in the serum could indicate the status of tissue p53 and P-gp. This could, therefore, be useful for screening for the most appropriate (lowest toxicity and highest effectiveness) drugs to use ahead of (neo)-adjuvant chemotherapy.

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p53 Modulation of DNA Topoisomerase IIα Gene Expression

Cited by 4 publications

References 36 publications

The effects of 1,4-benzoquinone on c-Myb and topoisomerase II in K-562 cells

The effects of 1,4-benzoquinone on c-Myb and topoisomerase II in K-562 cells

Identification of Promoter Elements Responsible for Transcriptional Inhibition of Polo-like Kinase 1 and Topoisomerase IIα Genes by p21^{WAF1/CIP1/ SDI1}

The Potential for Serum p53 to Predict the Response to Chemotherapy of Patients with Gastric Cancer

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p53 Modulation of DNA Topoisomerase IIα Gene Expression

Cited by 4 publications

References 36 publications

The effects of 1,4-benzoquinone on c-Myb and topoisomerase II in K-562 cells

The effects of 1,4-benzoquinone on c-Myb and topoisomerase II in K-562 cells

Identification of Promoter Elements Responsible for Transcriptional Inhibition of Polo-like Kinase 1 and Topoisomerase IIα Genes by p21WAF1/CIP1/ SDI1

The Potential for Serum p53 to Predict the Response to Chemotherapy of Patients with Gastric Cancer

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Identification of Promoter Elements Responsible for Transcriptional Inhibition of Polo-like Kinase 1 and Topoisomerase IIα Genes by p21^{WAF1/CIP1/ SDI1}