Ras activation of genes: Mob-1 as a model.
The ras oncogenes function by indirectly controlling expression of a subset of yet-undefined genes that are crucial for cell growth and differentiation. In a differential display strategy, numerous genes were identified on the basis of their differential expression in rat embryo fibroblasts transformed by the cooperation of mutant Ha-ras and p53 genes. We demonstrate here that one such gene, designated mob-1, is a downstream target of the Ras signaling pathway. The 417-bp mob-1 promoter, which contains dual NF-kappa B and AP-1 binding sites, confers the Ras inducibility. Oncogenic Ras as well as serum growth factors that activate endogenous Ras can induce mob-1 expression, but with a fundamental difference in that the oncogenic induction is constitutive whereas the serum induction is transient. mob-1 encodes a small secretory protein with a high degree of homology to IP-10, a member of a proinflammatory cytokine family. These findings link chronic inflammatory response to constitutive ras activation and tumorigenesis. Mob-1 may serve as a secreted marker for oncogenic Ha-ras mutations.
Liang
P
P
Division of Cell Growth and Regulation, Dana-Farber Cancer Institute, Boston, MA 02115.
Averboukh
L
L
Zhu
W
W
Pardee
A B
AB
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015415:Biomarkers; D002471:Cell Transformation, Neoplastic; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D003001:Cloning, Molecular; D016207:Cytokines / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D007249:Inflammation; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014018:Tissue Distribution; D015533:Transcriptional Activation
D015415:Biomarkers; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C091326:Cxcl10 protein, rat; D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger