biostudies-literatureSashida GNIDDK NIH HHS3687-99https://www.ebi.ac.uk/biostudies/studies/S-EPMC2698769biostudies-literatureUnknown29(13)Several ETS transcription factors, including ELF4/MEF, can function as oncogenes in murine cancer models and are overexpressed in human cancer. We found that Elf4/Mef activates Mdm2 expression; thus, lack of or knockdown of Elf4/Mef reduces Mdm2 levels in mouse embryonic fibroblasts (mef's), leading to enhanced p53 protein accumulation and p53-dependent senescence. Even though p53 is absent in Elf4(-/-) p53(-/-) mef's, neither oncogenic H-Ras(V12) nor c-myc can induce transformation of these cells. This appears to relate to the INK4a/ARF locus; both p19(ARF) and p16 are increased in Elf4(-/-) p53(-/-) mef's, and expression of Bmi-1 or knockdown of p16 in this context restores H-Ras(V12)-induced transformation. Thus, ELF4/MEF promotes tumorigenesis by inhibiting both the p53 and p16/Rb pathMolecular and cellular biologyELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to promote transformation.PMC2698769R01 DK052208R01 DK52208Liu YIzumi MSashida GMiyata YElf SOhyashiki KMenendez SNimer SDfalseELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to promote transformation.Several ETS transcription factors, including ELF4/MEF, can function as oncogenes in murine cancer models and are overexpressed in human cancer. We found that Elf4/Mef activates Mdm2 expression; thus, lack of or knockdown of Elf4/Mef reduces Mdm2 levels in mouse embryonic fibroblasts (mef's), leading to enhanced p53 protein accumulation and p53-dependent senescence. Even though p53 is absent in Elf4(-/-) p53(-/-) mef's, neither oncogenic H-Ras(V12) nor c-myc can induce transformation of these cells. This appears to relate to the INK4a/ARF locus; both p19(ARF) and p16 are increased in Elf4(-/-) p53(-/-) mef's, and expression of Bmi-1 or knockdown of p16 in this context restores H-Ras(V12)-induced transformation. Thus, ELF4/MEF promotes tumorigenesis by inhibiting both the p53 and p16/Rb path2009-01-01T00:00:00Z2009 Jul2025-04-19T10:30:25.627Z2019-03-27T00:23:02ZS-EPMC26987691938049010.1128/MCB.01551-0810.1128/mcb.01551-08