p53 Modulates Notch Signaling in MCF-7 Breast Cancer Cells by Associating With the Notch Transcriptional Complex Via MAML1
DC Field | Value | Language |
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dc.contributor.author | Yun, Jieun | - |
dc.contributor.author | Espinoza, Ingrid | - |
dc.contributor.author | Pannuti, Antonio | - |
dc.contributor.author | Romero, Damian | - |
dc.contributor.author | Martinez, Luis | - |
dc.contributor.author | Caskey, Mary | - |
dc.contributor.author | Stanculescu, Adina | - |
dc.contributor.author | Bocchetta, Maurizio | - |
dc.contributor.author | Rizzo, Paola | - |
dc.contributor.author | Band, Vimla | - |
dc.contributor.author | Band, Hamid | - |
dc.contributor.author | Kim, Hwan Mook | - |
dc.contributor.author | Park, Song-Kyu | - |
dc.contributor.author | Kang, Keon Wook | - |
dc.contributor.author | Avantaggiati, Maria Laura | - |
dc.contributor.author | Gomez, Christian R. | - |
dc.contributor.author | Golde, Todd | - |
dc.contributor.author | Osborne, Barbara | - |
dc.contributor.author | Miele, Lucio | - |
dc.date.available | 2020-02-28T07:41:38Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2015-12 | - |
dc.identifier.issn | 0021-9541 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/9856 | - |
dc.description.abstract | p53 and Notch-1 play important roles in breast cancer biology. Notch-1 inhibits p53 activity in cervical and breast cancer cells. Conversely, p53 inhibits Notch activity in T-cells but stimulates it in human keratinocytes. Notch co-activator MAML1 binds p53 and functions as a p53 co-activator. We studied the regulation of Notch signaling by p53 in MCF-7 cells and normal human mammary epithelial cells (HMEC). Results show that overexpression of p53 or activation of endogenous p53 with Nutlin-3 inhibits Notch-dependent transcriptional activity and Notch target expression in a dose-dependent manner. This effect could be partially rescued by transfection of MAML1 but not p300. Standard and quantitative co-immunoprecipitation experiments readily detected a complex containing p53 and Notch-1 in MCF-7 cells. Formation of this complex was inhibited by dominant negative MAML1 (DN-MAML1) and stimulated by wild-type MAML1. Standard and quantitative far-Western experiments showed a complex including p53, Notch-1, and MAML1. Chromatin immunoprecipitation (ChIP) experiments showed that p53 can associate with Notch-dependent HEY1 promoter and this association is inhibited by DN-MAML1 and stimulated by wild-type MAML1. Our data support a model in which p53 associates with the Notch transcriptional complex (NTC) in a MAML1-dependent fashion, most likely through a p53-MAML1 interaction. In our cellular models, the effect of this association is to inhibit Notch-dependent transcription. Our data suggest that p53-null breast cancers may lack this Notch-modulatory mechanism, and that therapeutic strategies that activate wild-type p53 can indirectly cause inhibition of Notch transcriptional activity. (C) 2015 Wiley Periodicals, Inc. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | WILEY-BLACKWELL | - |
dc.relation.isPartOf | JOURNAL OF CELLULAR PHYSIOLOGY | - |
dc.subject | STEM-CELLS | - |
dc.subject | NEGATIVE REGULATION | - |
dc.subject | ESTROGEN-RECEPTOR | - |
dc.subject | PATHWAY | - |
dc.subject | ACTIVATION | - |
dc.subject | TARGET | - |
dc.subject | MDM2 | - |
dc.subject | PROTEIN | - |
dc.subject | NUMB | - |
dc.subject | UBIQUITINATION | - |
dc.title | p53 Modulates Notch Signaling in MCF-7 Breast Cancer Cells by Associating With the Notch Transcriptional Complex Via MAML1 | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000360378000029 | - |
dc.identifier.doi | 10.1002/jcp.25052 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CELLULAR PHYSIOLOGY, v.230, no.12, pp.3115 - 3127 | - |
dc.identifier.scopusid | 2-s2.0-84939864823 | - |
dc.citation.endPage | 3127 | - |
dc.citation.startPage | 3115 | - |
dc.citation.title | JOURNAL OF CELLULAR PHYSIOLOGY | - |
dc.citation.volume | 230 | - |
dc.citation.number | 12 | - |
dc.contributor.affiliatedAuthor | Kim, Hwan Mook | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | STEM-CELLS | - |
dc.subject.keywordPlus | NEGATIVE REGULATION | - |
dc.subject.keywordPlus | ESTROGEN-RECEPTOR | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | TARGET | - |
dc.subject.keywordPlus | MDM2 | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | NUMB | - |
dc.subject.keywordPlus | UBIQUITINATION | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalResearchArea | Physiology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Physiology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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