Mutant p53 gain of function

• Verfasst von: Zalcenstein, Amir [VerfasserIn]
• Verfasst von: Müller-Schilling, Martina [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Titel: Mutant p53 gain of function
• Titelzusatz: repression of CD95(Fas/APO-1) gene expression by tumor-associated p53 mutants
• Verf.angabe: Amir Zalcenstein, Perry Stambolsky, Lilach Weisz, Martina Müller, David Wallach, Tanya M. Goncharov, Peter H. Krammer, Varda Rotter and Moshe Oren
• E-Jahr: 2003
• Jahr: 28 August 2003
• Umfang: 10 S.
• Teil: volume:22
• Teil: year:2003
• Teil: number:36
• Teil: pages:5667-5676
• Teil: extent:10
• Fussnoten: Gesehen am 07.04.2021
• Titel Quelle: Enthalten in: Oncogene
• Ort Quelle: London : Springer Nature, 1997
• Jahr Quelle: 2003
• Band/Heft Quelle: 22(2003), 36, Seite 5667-5676
• ISSN Quelle: 1476-5594
• DOI: doi:10.1038/sj.onc.1206724
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1753229863

Abstract

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.