| Autor: |
Zalcenstein, Amir, Stambolsky, Perry, Weisz, Lilach, Müller, Martina, Wallach, David, Goncharov, Tanya M, Krammer, Peter H, Rotter, Varda, Oren, Moshe |
| Předmět: |
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| Zdroj: |
Oncogene; 8/28/2003, Vol. 22 Issue 36, p5667-5676, 10p |
| Abstrakt: |
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.Oncogene (2003) 22, 5667-5676. doi:10.1038/sj.onc.1206724 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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