In:
Journal of Cell Science, The Company of Biologists
Abstract:
Concomitant expression of mutant p53 and oncogenic Ras, leading to cellular transformation, is well documented. However, the mechanisms by which the various mutant p53 categories cooperate with Ras remain largely obscure. In this study we suggest that different mutant p53 categories cooperate with H-Ras in different manners to induce a unique expression pattern of a cancer related gene signature (CGS). The DNA-contact p53 mutants (p53R248Q and p53R273H) exhibited the highest level of CGS expression by cooperating with NFκB. Furthermore, the Zn+2 region conformational p53 mutants (p53R175H and p53H179R) induced the CGS by elevating H-Ras activity. This elevation in H-Ras activity stemmed from a perturbed function of the p53 transcription target gene, BTG2. In contrast, the L3 loop region conformational mutant (p53G245S) did not affect the CGS expression. Our findings were further corroborated in human tumor-derived cell lines expressing Ras and the aforementioned mutated p53 proteins. These data might assist in future tailor-made therapy which targets the mutant p53-Ras axis in cancer.
Type of Medium:
Online Resource
ISSN:
1477-9137
,
0021-9533
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2012
detail.hit.zdb_id:
1410949-9
detail.hit.zdb_id:
1483099-1
SSG:
12