Your browser doesn't support javascript.
loading
Various p53 mutant proteins differently regulate the Ras circuit to induce a cancer-related gene signature.
Solomon, Hilla; Buganim, Yosef; Kogan-Sakin, Ira; Pomeraniec, Leslie; Assia, Yael; Madar, Shalom; Goldstein, Ido; Brosh, Ran; Kalo, Eyal; Beatus, Tsevi; Goldfinger, Naomi; Rotter, Varda.
Affiliation
  • Solomon H; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
J Cell Sci ; 125(Pt 13): 3144-52, 2012 Jul 01.
Article in En | MEDLINE | ID: mdl-22427690
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. From this study we suggest that different mutant p53 categories cooperate with H-Ras in different ways to induce a unique expression pattern of a cancer-related gene signature (CGS). The DNA-contact p53 mutants (p53(R248Q) and p53(R273H)) exhibited the highest level of CGS expression by cooperating with NFκB. Furthermore, the Zn(+2) region conformational p53 mutants (p53(R175H) and p53(H179R)) 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. By contrast, the L3 loop region conformational mutant (p53(G245S)) did not affect 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 targeting the mutant p53-Ras axis in cancer.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Regulation, Enzymologic / Gene Expression Regulation, Neoplastic / Tumor Suppressor Protein p53 / Genes, ras / Transcriptome Limits: Humans Language: En Journal: J Cell Sci Year: 2012 Type: Article Affiliation country: Israel

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Regulation, Enzymologic / Gene Expression Regulation, Neoplastic / Tumor Suppressor Protein p53 / Genes, ras / Transcriptome Limits: Humans Language: En Journal: J Cell Sci Year: 2012 Type: Article Affiliation country: Israel