ELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to promote transformation Journal Article
| Authors: | Sashida, G.; Liu, Y.; Elf, S.; Miyata, Y.; Ohyashiki, K.; Izumi, M.; Menendez, S.; Nimer, S. D. |
| Article Title: | ELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to promote transformation |
| Abstract: | 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<sup>-/-</sup> p53<sup>-/-</sup> mef's, neither oncogenic H-Ras<sub>V12</sub> nor c-myc can induce transformation of these cells. This appears to relate to the INK4a/ARF locus; both p19<sup>ARF</sup> and p16 are increased in Elf4<sup>-/-</sup> p53<sup>-/-</sup> mef's, and expression of Bmi-1 or knockdown of p16 in this context restores H-Ras<sup>V12</sup>-induced transformation. Thus, ELF4/MEF promotes tumorigenesis by inhibiting both the p53 and p16/Rb pathways. Copyright © 2009, American Society for Microbiology. All Rights Reserved. |
| Keywords: | cancer survival; controlled study; human tissue; protein expression; survival rate; unclassified drug; dna-binding proteins; proto-oncogene proteins; nonhuman; mouse; animals; mice; mice, knockout; animal tissue; cells, cultured; gene overexpression; protein p16; animal experiment; animal model; gene locus; protein p53; oncogene h ras; carcinogenesis; transcription factors; cell transformation, neoplastic; nuclear proteins; gene expression regulation; promoter regions, genetic; murinae; fibroblast; fibroblasts; tumor suppressor protein p53; senescence; protein p19; cyclin-dependent kinase inhibitor p16; genes, ras; oncogene c myc; malignant transformation; retinoblastoma protein; bmi1 protein; repressor proteins; cell aging; protein mdm2; transcription factor ets; proto-oncogene proteins c-mdm2; protein elf4 |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 29 |
| Issue: | 13 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2009-07-01 |
| Start Page: | 3687 |
| End Page: | 3699 |
| Language: | English |
| DOI: | 10.1128/mcb.01551-08 |
| PUBMED: | 19380490 |
| PROVIDER: | scopus |
| PMCID: | PMC2698769 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 30 November 2010" - "CODEN: MCEBD" - "Source: Scopus" |
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