Abstract:
:In this study, we show that silencing of CITED2 using small-hairpin RNA (shCITED2) induced DNA damage and reduction of ERCC1 gene expression in HEK293, HeLa and H1299 cells, even in the absence of cisplatin. In contrast, ectopic expression of ERCC1 significantly reduced intrinsic and induced DNA damage levels, and rescued the effects of CITED2 silencing on cell viability. The effects of CITED2 silencing on DNA repair and cell death were associated with p53 activity. Furthermore, CITED2 silencing caused severe elimination of the p300 protein and markers of relaxed chromatin (acetylated H3 and H4, i.e. H3K9Ac and H3K14Ac) in HEK293 cells. Chromatin immunoprecipitation assays further revealed that DNA damage induced binding of p53 along with H3K9Ac or H3K14Ac at the ERCC1 promoter, an effect which was almost entirely abrogated by silencing of CITED2 or p300. Moreover, lentivirus-based CITED2 silencing sensitized HeLa cell line-derived tumor xenografts to cisplatin in immune-deficient mice. These results demonstrate that CITED2/p300 can be recruited by p53 at the promoter of the repair gene ERCC1 in response to cisplatin-induced DNA damage. The CITED2/p300/p53/ERCC1 pathway is thus involved in the cell response to cisplatin and represents a potential target for cancer therapy.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Liu YC,Chang PY,Chao CCdoi
10.1093/nar/gkv934subject
Has Abstractpub_date
2015-12-15 00:00:00pages
10760-81issue
22eissn
0305-1048issn
1362-4962pii
gkv934journal_volume
43pub_type
杂志文章abstract::The FALC-Loop web server provides an online interface for protein loop modeling by employing an ab initio loop modeling method called FALC (fragment assembly and analytical loop closure). The server may be used to construct loop regions in homology modeling, to refine unreliable loop regions in experimental structures...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr352
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abstract::RNA editing in protozoan parasites is a mitochondrial RNA processing reaction in which exclusively uridylate residues are inserted into, and less frequently deleted from, pre-mRNAs. Molecules central to the process are so-called guide RNAs (gRNAs) which function as templates in the reaction. For a detailed molecular u...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.12.2311
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/30.7.1593
更新日期:2002-04-01 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.5.1265
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/23.8.1319
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks004
更新日期:2012-05-01 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/13.1.131
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt763
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abstract::Human immunodeficiency virus type 2 (HIV-2) reverse transcription is initiated from cellular tRNA(Lys3) partially annealed to the RNA viral genome at the primer binding site (PBS). This annealing involves interactions between two highly structured RNA molecules. In contrast to HIV-1, in which the reverse transcription...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.13.2757
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp1227
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gnh104
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw129
更新日期:2016-06-20 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1271
更新日期:2013-02-01 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1089
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abstract::We have previously reported that transcription from a distal promoter (promoter B) of the estrogen receptor alpha (ERalpha) gene is responsible for the increased expression of ERalpha in human breast carcinomas. This paper first characterized the promoter B region in terms of transient transfection experiments with lu...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.3.903
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.15.3219
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:2005-06-08 00:00:00