ZNF143 interacts with p73 and is involved in cisplatin resistance through the transcriptional regulation of DNA repair genes

Wakasugi, Tetsuro; Izumi, Hiroto; Uchiumi, Takeshi; Suzuki, Hideaki; Arao, Tokuzo; Nishio, Kazuto; Kohno, Kimitoshi

doi:10.1038/sj.onc.1210326

Cited by 53 publications

(91 citation statements)

References 26 publications

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“…previously described (10,20). Briefly, 250 pmol of siRNA and 5 μL of lipofectamine mixture were combined with 3.0 × 10 5 PC3 cells in 500 μL of culture medium and incubated for 20 minutes at room temperature.…”

Section: Knockdown Analysis Using Small Interfering Rnasmentioning

confidence: 99%

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Enhanced Expression of PCAF Endows Apoptosis Resistance in Cisplatin-Resistant Cells

Hirano

Izumi

Kidani

et al. 2010

Molecular Cancer Research

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Histone acetyltransferase (HAT) regulates transcription. We have previously shown that two HAT genes, Clock and Tip60, are overexpressed, and upregulate glutathione biosynthesis and the expression of DNA repair genes in cisplatin-resistant cells. To better understand the mechanism of HAT-related drug resistance, we investigated the role of another HAT gene, p300/CBP-associated factor (PCAF ), and found that PCAF was also overexpressed in cisplatin-resistant cells and endowed an antiapoptotic phenotype through enhanced E2F1 expression. PCAF-overexpressing cells showed enhanced expression of E2F1 and conferred cell resistance to chemotherapeutic agents. Downregulation of PCAF decreased E2F1 expression and sensitized cells to chemotherapeutic agents. Moreover, knockdown of PCAF induced G 1 arrest and apoptosis. These results suggest that PCAF is one of pleiotropic factors for drug resistance and seems to be critical for cancer cell growth. Mol Cancer Res; 8(6); 864-72. ©2010 AACR.

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Section: Knockdown Analysis Using Small Interfering Rnasmentioning

confidence: 99%

“…Whole-cell lysates were prepared as previously described (10,20). The indicated amounts of whole-cell lysates or nuclear extract were separated by SDS-PAGE and transferred to polyvinylidene difluoride microporous membranes (Millipore) using a semidry blotter.…”

Section: Western Blottingmentioning

confidence: 99%

Enhanced Expression of PCAF Endows Apoptosis Resistance in Cisplatin-Resistant Cells

Hirano

Izumi

Kidani

et al. 2010

Molecular Cancer Research

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“…Whole-cell lysates and nuclear extracts were prepared as described previously (Igarashi et al, 2007;Wakasugi et al, 2007). The indicated amounts of whole-cell lysates and nuclear extracts were separated by SDS-polyacrylamide gel electrophoresis (PAGE) and transferred to polyvinylidine difluoride microporous membranes (Millipore, Bedford, MA, USA) using a semidry blotter.…”

Section: Western Blotting Analysismentioning

confidence: 99%

“…Purification of GST-fusion proteins has been described previously (Igarashi et al, 2007;Wakasugi et al, 2007). GST-fusion proteins prepared as described above were bound to glutathione-sepharose 4B (GE Healthcare Bio-Science) in a 50% slurry in buffer X for 4 h at 4 1C, washed three times with buffer X and eluted with 50 mM Tris-HCl (pH 8.0) and 20 mM reduced glutathione according to the manufacturer's protocol (GE Healthcare Bio-Science).…”

Section: Purification Of Gst-fusion Proteinsmentioning

confidence: 99%

Twist and p53 reciprocally regulate target genes via direct interaction

et al. 2008

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“…17 Interestingly, the DNp73g-mediated transactivation is altered by the polymorphisms TP53 PIN3 and PEX4 (codon 72/R72P), which affect the basal activity of the internal TP53 promoter as already described. 23 This suggests a cooperation between DNp73g and another transcription factor that is able to bind to the response elements encompassing those two SNPs, such as ZNF143, known to interact with p73 protein, 33 and for which several predicted binding sites are overlapping with PIN3. 34 For p63b, we observed that p53RE-A1/A2 is not essential, whereas the region 753-1042 is required to obtain the maximal p63b-mediated transactivation.…”

Section: Discussionmentioning

confidence: 99%

Diverse p63 and p73 isoforms regulate Δ133p53 expression through modulation of the internal TP53 promoter activity

et al. 2011

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In response to stress, p53 binds and transactivates the internal TP53 promoter, thus regulating the expression of its own isoform, D133p53a. Here, we report that, in addition to p53, at least four p63/p73 isoforms regulate D133p53 expression at transcriptional level: p63b, DNp63a, DNp63b and DNp73c. This regulation occurs through direct DNA-binding to the internal TP53 promoter as demonstrated by chromatin immunoprecipitation and the use of DNA-binding mutant p63. The promoter regions involved in the p63/p73-mediated transactivation were identified using deleted, mutant and polymorphic luciferase reporter constructs. In addition, we observed that transient expression of p53 family members modulates endogenous D133p53a expression at both mRNA and protein levels. We also report concomitant variation of p63 and D133p53 expression during keratinocyte differentiation of HaCat cells and induced pluripotent stem cells derived from mutated p63 ectodermal dysplasia patients. Finally, proliferation assays indicated that D133p53a isoform regulates the anti-proliferative activities of p63b, DNp63a, DNp63b and DNp73c. Overall, this study shows a strong interplay between p53, p63 and p73 isoforms to orchestrate cell fate outcome. The TP53 family, composed of TP53, TP63 and TP73 genes, presents a strong homology of structures and expression patterns. 1,2 The three genes encode several protein isoforms carrying distinct N-termini (TA or D forms) and C-termini (a, b, g, y), because of the use of alternative promoters, splicing sites and translational initiation sites. 3,4 The full-length proteins also share a similar protein structure with a N-terminal transactivation domain, a central DNA-binding domain (DBD) and a C-terminal oligomerisation domain. 4,5 A strong interplay has been described between p53 family members. They all bind specifically to DNA response elements (p53RE), modulate gene expression and thus cellfate outcome. 6 Moreover, the p53-mediated apoptosis is severely impaired in the absence of p63 and p73 in response to DNA damage. 7 The interplay between p53 family members is not limited to transcriptional modulation of common target genes; they also regulate each other's expression and activity. 6 p53, p73 and DNp73 transactivate the promoter of DNp73 isoform, which in turn, inhibits the p53-and p73-mediated transcriptional activity and apoptosis through direct competition for DNAbinding. [8][9][10][11][12] Similarly, p53, DNp63 and p73g modulate the activity of the internal TP63 promoter regulating DNp63 expression, which inhibits p53, p63 and p73 transcriptional activities. 2,6,[13][14][15] Recently, it has been reported that p53 regulates the transcription of D133p53 isoform, which lacks the entire transactivation domain and part of the DBD. 16,17 p53 directly binds to p53REs located within the internal TP53 promoter leading to an increase of D133p53 mRNAs. Those transcripts generate two different N-terminal p53 isoforms, D133p53 and D160p53, through the use of two alternative translational initiation sites (co...

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ZNF143 interacts with p73 and is involved in cisplatin resistance through the transcriptional regulation of DNA repair genes

Cited by 53 publications

References 26 publications

Enhanced Expression of PCAF Endows Apoptosis Resistance in Cisplatin-Resistant Cells

Enhanced Expression of PCAF Endows Apoptosis Resistance in Cisplatin-Resistant Cells

Twist and p53 reciprocally regulate target genes via direct interaction

Diverse p63 and p73 isoforms regulate Δ133p53 expression through modulation of the internal TP53 promoter activity

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