Mutant p53 gain of function: repression of CD95(Fas/APO-1) gene expression by tumor-associated p53 mutants
Tumor-associated mutant forms of p53 can exert an antiapoptotic gain of function activity, which probably confers a selective advantage upon tumor cells harboring such mutations. We report that mutant p53 suppresses the expression of the CD95 (Fas/APO-1) gene, encoding a death receptor implicated in...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
28 August 2003
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| In: |
Oncogene
Year: 2003, Volume: 22, Issue: 36, Pages: 5667-5676 |
| ISSN: | 1476-5594 |
| DOI: | 10.1038/sj.onc.1206724 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/sj.onc.1206724 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/1206724 
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| Author Notes: | Amir Zalcenstein, Perry Stambolsky, Lilach Weisz, Martina Müller, David Wallach, Tanya M. Goncharov, Peter H. Krammer, Varda Rotter and Moshe Oren |
| Summary: | Tumor-associated mutant forms of p53 can exert an antiapoptotic gain of function activity, which probably confers a selective advantage upon tumor cells harboring such mutations. We report that mutant p53 suppresses the expression of the CD95 (Fas/APO-1) gene, encoding a death receptor implicated in a variety of apoptotic responses. Moderate (40-50%) downregulation of CD95 mRNA and surface protein expression by mutant p53 correlates with partial protection against CD95-dependent cell death. Excess mutant p53 represses the transcriptional activity of the CD95 promoter, with the extent of repression varying among different tumor-associated p53 mutants. Furthermore, mutant p53 protein binds the CD95 promoter in vitro, in a region distinct from the one implicated in tight interactions of the CD95 gene with wild-type p53. Hence, the CD95 promoter is likely to be a direct target for downregulation by mutant p53. This activity of mutant p53 may contribute to its gain of function effects in oncogenesis. |
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| Item Description: | Gesehen am 07.04.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1476-5594 |
| DOI: | 10.1038/sj.onc.1206724 |